| 1. |
- Ahlgren, Åsa Rydén, et al.
(författare)
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Response of the carotid artery longitudinal motion to submaximal physical activity in healthy humans-Marked changes already at low workload
- 2023
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Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 11:2
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Tidskriftsartikel (refereegranskat)abstract
- The longitudinal motion of the arterial wall, that is, the displacement of the arterial wall along the artery, parallel to blood flow, is still largely unexplored. The magnitude and nature of putative changes in longitudinal motion of the arterial wall in response to physical activity in humans remain unknown. The aim of this study was therefore to study the longitudinal motion of the carotid artery wall during physical activity in healthy humans. Using in-house developed non-invasive ultrasonic methods, the longitudinal motion of the intima-media complex and the diameter changes of the right common carotid artery (CCA) in 40 healthy volunteers (20 volunteers aged 22-35 years; 20 volunteers aged 55-68 years) were assessed at rest and during submaximal supine bicycle exercise. In a subset of the subjects (n = 18) also intramural shear strain were analyzed. The longitudinal motion of the intima-media complex underwent marked changes in response to physical activity, already at low workload; with most evident a marked increase of the first antegrade displacement (p < 0.001) in early systole. Likewise, the corresponding shear strain also increased significantly (p = 0.004). The increase in longitudinal motion showed significant correlation to increase in blood pressure, but not to blood flow velocity or wall shear stress. In conclusion, physical activity markedly influences the longitudinal motion of the carotid artery wall in healthy humans already at low load. A possible "cushioning" function as well as possible implications for the function of the vasa vasorum, endothelium, and smooth muscle cells and extracellular matrix of the media, are discussed.
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| 2. |
- Bakker, G. J., et al.
(författare)
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Oral vancomycin treatment does not alter markers of postprandial inflammation in lean and obese subjects
- 2019
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Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 7:16
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Tidskriftsartikel (refereegranskat)abstract
- Intake of a high-fat meal induces a systemic inflammatory response in the postprandial which is augmented in obese subjects. However, the underlying mechanisms of this response have not been fully elucidated. We aimed to assess the effect of gut microbiota modulation on postprandial inflammatory response in lean and obese subjects. Ten lean and ten obese subjects with metabolic syndrome received oral vancomycin 500 mg four times per day for 7 days. Oral high-fat meal tests (50 g fat/m(2) body surface area) were performed before and after vancomycin intervention. Gut microbiota composition, leukocyte counts, plasma lipopolysaccharides (LPS), LPS-binding protein (LBP), IL-6 and MCP-1 concentrations and monocyte CCR2 and cytokine expression were determined before and after the high-fat meal. Oral vancomycin treatment resulted in profound changes in gut microbiota composition and significantly decreased bacterial diversity in both groups (phylogenetic diversity pre- versus post-intervention: lean, 56.9 +/- 7.8 vs. 21.4 +/- 6.6, P < 0.001; obese, 53.9 +/- 7.8 vs. 21.0 +/- 5.9, P < 0.001). After intervention, fasting plasma LPS significantly increased (lean, median [IQR] 0.81 [0.63-1.45] EU/mL vs. 2.23 [1.33-3.83] EU/mL, P = 0.017; obese, median [IQR] 0.76 [0.45-1.03] EU/mL vs. 1.44 [1.11-4.24], P = 0.014). However, postprandial increases in leukocytes and plasma LPS were unaffected by vancomycin in both groups. Moreover, we found no changes in plasma LBP, IL-6 and MCP-1 or in monocyte CCR2 expression. Despite major vancomycin-induced disruption of the gut microbiota and increased fasting plasma LPS, the postprandial inflammatory phenotype in lean and obese subjects was unaffected in this study.
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| 3. |
- Bhattachariya, Anirban, et al.
(författare)
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PYK2 selectively mediates signals for growth versus differentiation in response to stretch of spontaneously active vascular smooth muscle.
- 2014
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Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 2:7
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Tidskriftsartikel (refereegranskat)abstract
- Stretch of vascular smooth muscle stimulates growth and proliferation as well as contraction and expression of contractile/cytoskeletal proteins, all of which are also regulated by calcium-dependent signals. We studied the role of the calcium- and integrin-activated proline-rich tyrosine kinase 2 (PYK2) in stretch-induced responses of the rat portal vein loaded by a hanging weight ex vivo. PYK2 phosphorylation at Tyr-402 was increased both by a 10-min stretch and by organ culture with load over several days. Protein and DNA synthesis were reduced by the novel PYK2 inhibitor PF-4594755 (0.5-1 μmol/L), while still sensitive to stretch. In 3-day organ culture, PF-4594755 caused maintained myogenic spontaneous activity but did not affect contraction in response to high-K(+) (60 mmol/L) or to α1-adrenergic stimulation by cirazoline. Basal and stretch-induced PYK2 phosphorylation in culture were inhibited by PF-4594755, closely mimicking inhibition of non-voltage-dependent calcium influx by 2-APB (30 μmol/L). In contrast, the L-type calcium channel blocker, nifedipine (1 μmol/L) eliminated stretch-induced but not basal PYK2 phosphorylation. Stretch-induced Akt and ERK1/2 phosphorylation was eliminated by PF-4594755. PYK2 inhibition had no effect on mRNA expression of several smooth muscle markers, and stretch-sensitive SM22α synthesis was preserved. Culture of portal vein with the Ang II inhibitor losartan (1 μmol/L) eliminated stretch sensitivity of PYK2 and Akt phosphorylation, but did not affect mRNA expression of smooth muscle markers. The results suggest that PYK2 signaling functionally distinguishes effects of voltage- and non-voltage-dependent calcium influx. A small-molecule inhibitor of PYK2 reduces growth and DNA synthesis but does not affect contractile differentiation of vascular smooth muscle.
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| 4. |
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| 5. |
- Boon, Hanneke, 1981-, et al.
(författare)
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MicroRNA-208b progressively declines after spinal cord injury in humans and is inversely related to myostatin expression
- 2015
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Ingår i: Physiological Reports. - Chichester : John Wiley & Sons. - 2051-817X. ; 3:11
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Tidskriftsartikel (refereegranskat)abstract
- The effects of long‐term physical inactivity on the expression of microRNAs involved in the regulation of skeletal muscle mass in humans are largely unknown. MicroRNAs are short, noncoding RNAs that fine‐tune target expression through mRNA degradation or by inhibiting protein translation. Intronic to the slow, type I, muscle fiber type genes MYH7 and MYH7b, microRNA‐208b and microRNA‐499‐5p are thought to fine‐tune the expression of genes important for muscle growth, such as myostatin. Spinal cord injured humans are characterized by both skeletal muscle atrophy and transformation toward fast‐twitch, type II fibers. We determined the expression of microRNA‐208b, microRNA‐499‐5p, and myostatin in human skeletal muscle after complete cervical spinal cord injury. We also determined whether these microRNAs altered myostatin expression in rodent skeletal muscle. A progressive decline in skeletal muscle microRNA‐208b and microRNA‐499‐5p expression occurred in humans during the first year after spinal cord injury and with long‐standing spinal cord injury. Expression of myostatin was inversely correlated with microRNA‐208b and microRNA‐499‐5p in human skeletal muscle after spinal cord injury. Overexpression of microRNA‐208b in intact mouse skeletal muscle decreased myostatin expression, whereas microRNA‐499‐5p was without effect. In conclusion, we provide evidence for an inverse relationship between expression of microRNA‐208b and its previously validated target myostatin in humans with severe skeletal muscle atrophy. Moreover, we provide direct evidence that microRNA‐208b overexpression decreases myostatin gene expression in intact rodent muscle. Our results implicate that microRNA‐208b modulates myostatin expression and this may play a role in the regulation of skeletal muscle mass following spinal cord injury. © 2015 The Authors
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| 6. |
- Cardinale, Daniele A, et al.
(författare)
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Reliability of maximal mitochondrial oxidative phosphorylation in permeabilized fibers from the vastus lateralis employing high-resolution respirometry.
- 2018
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Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 6:4
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Tidskriftsartikel (refereegranskat)abstract
- The purpose was to assess the impact of various factors on methodological errors associated with measurement of maximal oxidative phosphorylation (OXPHOS) in human skeletal muscle determined by high-resolution respirometry in saponin-permeabilized fibers. Biopsies were collected from 25 men to assess differences in OXPHOS between two muscle bundles and to assess the correlation between OXPHOS and the wet weight of the muscle bundle. Biopsies from left and right thighs of another five subjects were collected on two occasions to compare limbs and time-points. A single muscle specimen was used to assess effects of the anesthetic carbocaine and the influence of technician. The difference in OXPHOS between two fiber-bundles from the same biopsy exhibited a standard error of measurement (SEM) of 10.5 pmol · s-1 · mg-1 and a coefficient of variation (CV) of 15.2%. The differences between left and right thighs and between two different time-points had SEMs of 9.4 and 15.2 pmol · s-1 · mg-1 and CVs of 23.9% and 33.1%, respectively. The average (±SD) values obtained by two technicians monitoring different bundles of fibers from the same biopsy were 31.3 ± 7.1 and 26.3 ± 8.1 pmol · s-1 · mg-1 . The time that elapsed after collection of the biopsy (up to a least 5 h in preservation medium), wet weight of the bundle (from 0.5 to 4.5 mg) and presence of an anesthetic did not influence OXPHOS. The major source of variation in OXPHOS measurements is the sample preparation. The thigh involved, time-point of collection, size of fiber bundles, and time that elapsed after biopsy had minor or no effect.
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| 7. |
- Carlén, Anna, 1985-, et al.
(författare)
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ST/HR variables in firefighter exercise ECG : relation to ischemic heart disease
- 2019
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Ingår i: Physiological Reports. - : John Wiley & Sons. - 2051-817X. ; 7:2
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Tidskriftsartikel (refereegranskat)abstract
- Exercise electrocardiography (ExECG) is regularly performed by Swedish firefighters by law. Heart rate-corrected analysis of ST segment variables (ST/HR) has shown improved prediction of ischemic heart disease (IHD) compared to ST depression alone. This has not previously been extensively studied in asymptomatic persons with a low probability of IHD. We therefore evaluated the predictive performance of ST/HR analysis in firefighter ExECG. ExECG was studied in 521 male firefighters. During 8.4 ± 2.1 years, 2.3% (n = 12) were verified with IHD by catheterization or myocardial scintigraphy (age 51.5 ± 5.5 years) and were compared with firefighters without imaging proof of IHD (44.2 ± 10.1 years). The predictive value of ST depression, ST/HR index, ST/HR slope, and area and rotation of the ST/HR loop was calculated as age-adjusted odds ratios (OR), in 10 ECG leads. Predictive accuracy was analyzed with receiver operating characteristics (ROC) analysis. ST/HR index ≤-1.6 μV/bpm and ST/HR slope ≤-2.4 μV/bpm were associated with increased IHD risk in three individual leads (all OR > 1.0, P < 0.05). ST/HR loop area lower than the fifth percentile of non-IHD subjects indicated IHD risk in V4, V5, aVF, II, and -aVR (P < 0.05). ST depression ≤-0.1 mV was associated with IHD only in V4 (OR, 9.6, CI, 2.3-40.0). ROC analysis of each of these variables yielded areas under the curve of 0.72 or lower for all variables and leads. Clockwise-rotated ST/HR loops was associated with increased risk in most leads compared to counterclockwise rotation. The limited clinical value of ExECG in low-risk populations was emphasized, but if performed, ST/HR analysis should probably be given more importance.
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| 8. |
- Casselbrant, Anna, 1970, et al.
(författare)
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Asymmetric mucosal structure, mesenteric versus antimesenteric, in mouse, rat, and human small intestines
- 2022
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Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 10:24
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Tidskriftsartikel (refereegranskat)abstract
- The morphology of the small intestinal mucosa is reflected by the degree of stimuli. Previous studies have come to different conclusion about whether the mucosa is equally symmetrical. The aim of the study is to investigate whether there are structural differences in the mesenteric versus antimesenteric mucosa in mice, rats, and humans. Jejunal biopsies from mice and rats were saved. Samples from human small intestine were obtained from patients undergoing Roux-en-Y gastric bypass surgery. Fixed samples were used to morphologically evaluate villus height and enlargement factor due to villi. The number of goblet cells, mast cells, enteroendocrine cells, and Paneth cells were histologically analyzed in the villus structure. Cell turnover was analyzed by Ki-67 staining. There was a significant increased villi height and villus enlargement factor antimesenterically in mice, rats, and human small intestines. The distribution of goblet cells, mast cells, and Paneth cells were equal while the number of enteroendocrine cells was increased antimesenteric in the human samples. The crypt mitotic activity was almost 20% higher in the antimesenteric part of jejunum. In summary we found longer villi, greater surface enlargement, and increased number of enteroendocrine cells as well as increased cell turnover antimesenterically. These differences may be of importance in understanding normal gastrointestinal physiology in health and disease.
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| 9. |
- Chaillou, Thomas, 1985-, et al.
(författare)
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Docetaxel does not impair skeletal muscle force production in a murine model of cancer chemotherapy
- 2017
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Ingår i: Physiological Reports. - : American Physiological Society. - 2051-817X. ; 5:11
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Tidskriftsartikel (refereegranskat)abstract
- Chemotherapy drugs such as docetaxel are commonly used to treat cancer. Cancer patients treated with chemotherapy experience decreased physical fitness, muscle weakness and fatigue. To date, it is unclear whether these symptoms result only from cancer-derived factors or from the combination of cancer disease and cancer treatments, such as chemotherapy. In this study, we aimed at determining the impact of chemotherapy per se on force production of hind limb muscles from healthy mice treated with docetaxel. We hypothesized that docetaxel will decrease maximal force, exacerbate the force decline during repeated contractions and impair recovery after fatiguing stimulations. We examined the function of soleus and extensor digitorum longus (EDL) muscles 24h and 72h after a single injection of docetaxel (acute treatment), and 7days after the third weekly injection of docetaxel (repeated treatment). Docetaxel was administrated by intravenous injection (20mg/kg) in female FVB/NRj mice and control mice were injected with saline solution. Our results show that neither acute nor repeated docetaxel treatment significantly alters force production during maximal contractions, repeated contractions or recovery. Only a tendency to decreased peak specific force was observed in soleus muscles 24h after a single injection of docetaxel (-17%, P=0.13). In conclusion, docetaxel administered intravenously does not impair force production in hind limb muscles from healthy mice. It remains to be clarified whether docetaxel, or other chemotherapy drugs, affect muscle function in subjects with cancer and whether the side effects associated with chemotherapy (neurotoxicity, central fatigue, decreased physical activity, etc.) are responsible for the experienced muscle weakness and fatigue.
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| 10. |
- Dahlberg, Pia, et al.
(författare)
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Accelerated QT adaptation following atropine-induced heart rate increase in LQT1 patients versus healthy controls: A sign of disturbed hysteresis.
- 2022
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Ingår i: Physiological reports. - : Wiley. - 2051-817X. ; 10:21
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Tidskriftsartikel (refereegranskat)abstract
- Hysteresis, a ubiquitous regulatory phenomenon, is a salient feature of the adaptation of ventricular repolarization duration to heart rate (HR) change. We therefore compared the QT interval adaptation to rapid HR increase in patients with the long QT syndrome type 1 (LQT1) versus healthy controls because LQT1 is caused by loss-of-function mutations affecting the repolarizing potassium channel current IKs , presumably an important player in QT hysteresis. The study was performed in an outpatient hospital setting. HR was increased in LQT1 patients and controls by administering an intravenous bolus of atropine (0.04mg/kg body weight) for 30s. RR and QT intervals were recorded by continuous Frank vectorcardiography. Atropine induced transient expected side effects but no adverse arrhythmias. There was no difference in HR response (RR intervals) to atropine between the groups. Although atropine-induced ΔQT was 48% greater in 18 LQT1 patients than in 28 controls (p<0.001), QT adaptation was on average 25% faster in LQT1 patients (measured as the time constant τ for the mono-exponential function and the time for 90% of ΔQT; p<0.01); however, there was some overlap between the groups, possibly a beta-blocker effect. The shorter QT adaptation time to atropine-induced HR increase in LQT1 patients on the group level corroborates the importance of IKs in QT adaptation hysteresis in humans and shows that LQT1 patients have a disturbed ultra-rapid cardiac memory. On the individual level, the QT adaptation time possibly reflects the effect-size of the loss-of-function mutation, but its clinical implications need to be shown.
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| 11. |
- de Git, K. C. G., et al.
(författare)
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Rats that are predisposed to excessive obesity show reduced (leptin-induced) thermoregulation even in the preobese state
- 2019
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Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 7:14
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Tidskriftsartikel (refereegranskat)abstract
- Both feeding behavior and thermogenesis are regulated by leptin. The sensitivity to leptin's anorexigenic effects on chow diet was previously shown to predict the development of diet-induced obesity. In this study, we determined whether the sensitivity to leptin's anorexigenic effects correlates with leptin's thermogenic response, and if this response is exerted at the level of the dorsomedial hypothalamus (DMH), a brain area that plays an important role in thermoregulation. Based on the feeding response to injected leptin on a chow diet, rats were divided into leptin-sensitive (LS) and leptin-resistant (LR) groups. The effects of leptin on core body, brown adipose tissue (BAT) and tail temperature were compared after intravenous versus intra-DMH leptin administration. After intravenous leptin injection, LS rats increased their BAT thermogenesis and reduced heat loss via the tail, resulting in a modest increase in core body temperature. The induction of these thermoregulatory mechanisms with intra-DMH leptin was smaller, but in the same direction as with intravenous leptin administration. In contrast, LR rats did not show any thermogenic response to either intravenous or intra-DMH leptin. These differences in the thermogenic response to leptin were associated with a 1°C lower BAT temperature and reduced UCP1 expression in LR rats under adlibitum feeding. The preexisting sensitivity to the anorexigenic effects of leptin, a predictor for obesity, correlates with the sensitivity to the thermoregulatory effects of leptin, which appears to be exerted, at least in part, at the level of the DMH. © 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.
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| 12. |
- Dolinina, Julia, et al.
(författare)
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Clemizole and La3+ salts ameliorate angiotensin II-induced glomerular hyperpermeability in vivo
- 2021
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Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 9:10
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Tidskriftsartikel (refereegranskat)abstract
- Angiotensin II (Ang II) induces marked, dynamic increases in the permeability of the glomerular filtration barrier (GFB) in rats. After binding to its receptor, Ang II elicits Ca2+ influx into cells, mediated by TRPC5 and TRPC6 (transient receptor potential canonical type 5 and 6). Clemizole and La3+ salts have been shown to block TRPC channels in vitro, and we therefore tested their potential effect on Ang II-induced glomerular hyperpermeability. Anesthetized male Sprague-Dawley rats were infused with Ang II (80 ng kg–1min–1) alone, or together with clemizole or low-dose La3+ (activates TRPC5, blocks TRPC6) or high-dose La3+ (blocks both TRPC5 and TRPC6). Plasma and urine samples were taken during baseline and at 5 min after the start of the infusions and analyzed by high-performance size-exclusion chromatography for determination of glomerular sieving coefficients for Ficoll 10–80 Å (1–8 nm). Ang II infusion evoked glomerular hyperpermeability to large Ficolls (50–80 Å), which was ameliorated by clemizole, having no significant effect on glomerular filtration rate (GFR) or Ang II-mediated increase in mean arterial pressure (ΔMAP). In contrast, high- and low-dose La3+ significantly lowered ΔMAP and reduced Ang II-induced hyperpermeability. Combined, clemizole and low-dose La3+ were less effective at ameliorating Ang II-induced glomerular hyperpermeability than low-dose La3+ alone. In conclusion, our data show that both clemizole and La3+ are effective against Ang II-induced glomerular hyperpermeability, with differential effects on blood pressure. Further research using more specific blockers of TRPC5 and TRPC6 should be performed to reveal the underlying mechanisms.
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| 13. |
- Emanuelsson, Eric B., et al.
(författare)
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MRI characterization of skeletal muscle size and fatty infiltration in long--term trained and untrained individuals
- 2022
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Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 54:9, s. 389-389
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated body composition measures in highly trained and untrained individuals using whole--body magnetic resonance imaging (MRI). Additionally, correlations between these measures and skeletal muscle gene expression were performed. Thirty-six individuals were included: endurance-trained males (ME, n = 8) and females (FE, n = 7), strength-trained males (MS, n = 7), and untrained control males (MC, n = 8) and females (FC, n = 6). MRI scans were performed, and resting M. vastus lateralis (VL) biopsies were subjected to RNA sequencing. Liver fat fraction, visceral adipose tissue volume (VAT), total body fat, and total lean tissue were measured from MRI data. Additionally, cross-sectional area (CSA) and fat signal fraction (FSF) were calculated from Mm. pectoralis, M. erector spinae and M. multifidus combined, Mm. quadriceps, and Mm. triceps surae (TS). Liver fat fraction, VAT, and total body fat relative to body weight were lower in ME and FE compared with corresponding controls. MS had a larger CSA across all four muscle groups and lower FSF in all muscles apart from TS compared with MC. ME had a lower FSF across all muscle groups and a larger CSA in all muscles except TS than MC. FE athletes showed a higher CSA in Mm. pectoralis and Mm. quadriceps and a lower CSA in TS than FC with no CSA differences found in the back muscles investigated. Surprisingly, the only difference in FSF between FE and FC was found in Mm. pectoralis. Lastly, correlations between VL gene expression and VL CSA as well as FSF showed that genes positively correlated with CSA revealed an enrichment of the oxidative phosphorylation and thermogenesis pathways, while the genes positively correlated with FSF showed significant enrichment of the spliceosome pathway. Although limited differences were found with training in females, our study suggests that both regular endurance and resistance training are useful in maintaining muscle mass, reducing adipose tissue deposits, and reducing muscle fat content in males.
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| 14. |
- Erdling, André, et al.
(författare)
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Changes in P2Y6 receptor-mediated vasoreactivity following focal and global ischemia
- 2022
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Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 10:8
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Tidskriftsartikel (refereegranskat)abstract
- Ischemia, both in the form of focal thromboembolic stroke and following subarachnoid hemorrhage (SAH), causes upregulation of vasoconstrictive receptor systems within the cerebral vasculature. Descriptions regarding changes in purinergic signaling following ischemia are lacking, especially when the importance of purinergic signaling in regulating vascular tone is taken into consideration. This prompted us to evaluate changes in P2Y6-mediated vasomotor reactivity in two different stroke models in rat. We used wire myography to measure changes in cerebral vasoreactivity to the P2Y6 agonist UDP-β-S following either experimental SAH or transient middle cerebral artery occlusion. Changes in receptor localization or receptor expression were evaluated using immunohistochemistry and quantitative flow cytometry. Transient middle cerebral artery occlusion caused an increase in Emax when compared to sham (233.6 [206.1–258.5]% vs. 161.1 [147.1–242.6]%, p = 0.0365). No such change was seen following SAH. Both stroke models were associated with increased levels of P2Y6 receptor expression in the vascular smooth muscle cells (90.94 [86.99–99.15]% and 93.79 [89.96–96.39]% vs. 80.31 [70.80–80.86]%, p = 0.021) and p = 0.039 respectively. There was no change in receptor localization in either of the stroke models. Based on these findings, we conclude that focal ischemic stroke increases vascular sensitivity to UDP-β-S by upregulating P2Y6 receptors on vascular smooth muscle cells while experimental SAH did not induce changes in vasoreactivity in spite of increased P2Y6 receptor expression.
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| 15. |
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| 16. |
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| 17. |
- Farooqi, Nighat, et al.
(författare)
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Validation of SenseWear Armband and ActiHeart monitors for assessments of daily energy expenditure in free-living women with chronic obstructive pulmonary disease
- 2013
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Ingår i: Physiological Reports. - : The American Physiological Society. - 2051-817X. ; 1:6
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Tidskriftsartikel (refereegranskat)abstract
- To provide individually adapted nutritional support to patients with chronic obstructive pulmonary disease (COPD), objective and reliable methods must be used to assess patient energy requirements. The aim of this study was to validate the use of SenseWear Armband (SWA) and ActiHeart (AH) monitors for assessing total daily energy expenditure (TEE) and activity energy expenditure (AEE) and compare these techniques with the doubly labeled water (DLW) method in free‐living women with COPD. TEE and AEE were measured in 19 women with COPD for 14 days using SWAs with software version 5.1 (TEESWA5, AEESWA5) or 6.1 (TEESWA6, AEESWA6) and AH monitors (TEEAH, AEEAH), using DLW (TEEDLW) as the criterion method. The three methods were compared using intraclass correlation coefficient (ICC) and Bland–Altman analyses. The mean TEE did not significantly differ between the DLW and SWA5.1 methods (−21 ± 726 kJ/day; P = 0.9), but it did significantly differ between the DLW and SWA6.1 (709 ± 667 kJ/day) (P < 0.001) and the DLW and AH methods (709 ± 786 kJ/day) (P < 0.001). Strong agreement was observed between the DLW and TEESWA5 methods (ICC = 0.76; 95% CI 0.47–0.90), with moderate agreements between the DLW and TEESWA6 (ICC = 0.66; 95% CI 0.02–0.88) and the DLW and TEEAH methods (ICC = 0.61; 95% CI 0.05–0.85). Compared with the DLW method, the SWA5.1 underestimated AEE by 12% (P = 0.03), whereas the SWA6.1 and AH monitors underestimated AEE by 35% (P < 0.001). Bland–Altman plots revealed no systematic bias for TEE or AEE. The SWA5.1 can reliably assess TEE in women with COPD. However, the SWA6.1 and AH monitors underestimate TEE. The SWA and AH monitors underestimate AEE.
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| 18. |
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| 19. |
- Gao, Xiang, et al.
(författare)
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Effects of GIP on regional blood flow during normoglycemia and hyperglycemia in anesthetized rats
- 2018
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Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 6:8
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Tidskriftsartikel (refereegranskat)abstract
- The incretin hormone glucose-dependent insulinotropic polypeptide (GIP) potentiates glucose-stimulated insulin secretion, and affects -cell turnover. This study aimed at evaluating if some of the beneficial effects of GIP on glucose homeostasis can be explained by modulation of islet blood flow. Anesthetized Sprague-Dawley rats were infused intravenously with different doses of GIP (10, 20, or 60ng/kg*min) for 30min. Subsequent organ blood flow measurements were performed with microspheres. In separate animals, islets were perfused exvivo with GIP (10(-6)-10(-12)mol/L) during normo- and hyperglycemia and arteriolar responsiveness was recorded. The highest dose of GIP potentiated insulin secretion during hyperglycemia, but had no effect in normoglycemic rats. The highest GIP concentration decreased blood perfusion of whole pancreas, pancreatic islets, duodenum, colon, liver and kidneys. The decrease in blood flow was unaffected by ganglion blockade or adenosine receptor inhibition. In contrast to this, in single perfused islets GIP induced a dose-dependent arteriolar dilation. Thus, high doses of GIP exert a direct dilatory effect on islet arterioles in isolated islets, but induce a generalized vasoconstriction in splanchnic organs, including the whole pancreas and islets, invivo. The latter effect is unlikely to be mediated by adenosine, the autonomic nervous system, or endothelial mediators.
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| 20. |
- Gejl, Kasper D., et al.
(författare)
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Changes in metabolism but not myocellular signaling by training with CHO-restriction in endurance athletes
- 2018
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Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 6:17
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Tidskriftsartikel (refereegranskat)abstract
- Carbohydrate (CHO) restricted training has been shown to increase the acute training response, whereas less is known about the acute effects after repeated CHO restricted training. On two occasions, the acute responses to CHO restriction were examined in endurance athletes. Study 1 examined cellular signaling and metabolic responses after seven training-days including CHO manipulation (n = 16). The protocol consisted of 1 h high-intensity cycling, followed by 7 h recovery, and 2 h of moderate-intensity exercise (120SS). Athletes were randomly assigned to low (LCHO: 80 g) or high (HCHO: 415 g) CHO during recovery and the 120SS. Study 2 examined unaccustomed exposure to the same training protocol (n = 12). In Study 1, muscle biopsies were obtained at rest and 1 h after 120SS, and blood samples drawn during the 120SS. In Study 2, substrate oxidation and plasma glucagon were determined. In Study 1, plasma insulin and proinsulin C-peptide were higher during the 120SS in HCHO compared to LCHO (insulin: 0 min: +37%; 60 min: +135%; 120 min: +357%, P = 0.05; proinsulin C-peptide: 0 min: +32%; 60 min: +52%; 120 min: +79%, P = 0.02), whereas plasma cholesterol was higher in LCHO (+15-17%, P = 0.03). Myocellular signaling did not differ between groups. p-AMPK and p-ACC were increased after 120SS (+35%, P = 0.03; +59%, P = 0.0004, respectively), with no alterations in p-p38, p-53, or p-CREB. In Study 2, glucagon and fat oxidation were higher in LCHO compared to HCHO during the 120SS (+26-40%, P = 0.03; +44-76%, P = 0.01 respectively). In conclusion, the clear respiratory and hematological effects of CHO restricted training were not translated into superior myocellular signaling after accustomization to CHO restriction.
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| 21. |
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| 22. |
- Gidlund, Eva-Karin, et al.
(författare)
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Humanin skeletal muscle protein levels increase after resistance training in men with impaired glucose metabolism
- 2016
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Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 4:23
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Tidskriftsartikel (refereegranskat)abstract
- Humanin (HN) is a mitochondrially encoded and secreted peptide linked to glucose metabolism and tissue protecting mechanisms. Whether skeletal muscle HN gene or protein expression is influenced by exercise remains unknown. In this intervention study we show, for the first time, that HN protein levels increase in human skeletal muscle following 12 weeks of resistance training in persons with prediabetes. Male subjects (n = 55) with impaired glucose regulation (IGR) were recruited and randomly assigned to resistance training, Nordic walking or a control group. The exercise interventions were performed three times per week for 12 weeks with progressively increased intensity during the intervention period. Biopsies from the vastus lateralis muscle and venous blood samples were taken before and after the intervention. Skeletal muscle and serum protein levels of HN were analyzed as well as skeletal muscle gene expression of the mitochondrially encoded gene MT-RNR2, containing the open reading frame for HN. To elucidate mitochondrial training adaptation, mtDNA, and nuclear DNA as well as Citrate synthase were measured. Skeletal muscle HN protein levels increased by 35% after 12 weeks of resistance training. No change in humanin protein levels was seen in serum in any of the intervention groups. There was a significant correlation between humanin levels in serum and the improvements in the 2 h glucose loading test in the resistance training group. The increase in HN protein levels in skeletal muscle after regular resistance training in prediabetic males may suggest a role for HN in the regulation of glucose metabolism. Given the preventative effect of exercise on diabetes type 2, the role of HN as a mitochondrially derived peptide and an exercise-responsive mitokine warrants further investigation.
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| 23. |
- Gottlieb, Lisa A, et al.
(författare)
-
Translational implications of bradyarrhythmia in hibernating brown bears
- 2023
-
Ingår i: Physiological Reports. - : John Wiley & Sons. - 2051-817X. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- The brown bear Ursus arctos undergoes exceptional physiological adaptions during annual hibernation that minimize energy consumption, including profound decrease in heart rate, cardiac output, and respiratory rate. These changes are completely reversible after the bears reenter into the active state in spring. In this case report, we show episodes of sinus arrest in a hibernating Scandinavian brown bear and in humans, recorded by implantable loop recorders and discuss the possible underlying mechanisms. Lessons learned from cardiac adaptations in hibernating bears might prove useful in the treatment of patients with sinus node dysfunction.
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| 24. |
- Gouveia, Leonor, et al.
(författare)
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Expression analysis of platelet-derived growth factor receptor alpha and its ligands in the developing mouse lung
- 2017
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Ingår i: Physiological Reports. - : WILEY. - 2051-817X. ; 5:6
-
Tidskriftsartikel (refereegranskat)abstract
- Activation of the platelet-derived growth factor receptor-a (PDGFRa) signaling pathway is critically important during lung alveogenesis, the process in lung development during which alveoli are formed from the terminal alveolar sacs. Several studies have aimed to characterize the expression patterns of PDGFRa and its two ligands (PDGF-A and -C) in the lung, but published analyses have been limited to embryonic and/or perinatal time points, and no attempts have been made to characterize both receptor and ligand expression simultaneously. In this study, we present a detailed map of the expression patterns of PDGFRa, PDGF-A and PDGF-C during the entire period of lung development, that is, from early embryogenesis until adulthood. Three different reporter mice were analyzed (Pdgfa ex4-COIN-INV-lacZ, Pdgfc tm1Nagy, and Pdgfra tm11(EGFP) Sor), in which either lacZ or H2B-GFP were expressed under the respective promoter in gene-targeted alleles. A spatiotemporal dynamic expression was identified for both ligands and receptor. PDGF-A and PDGF-C were located to distinct populations of epithelial and smooth muscle cells, whereas PDGFRa expression was located to different mesenchymal cell populations. The detailed characterization of gene expression provides a comprehensive map of PDGFRa signaling in lung cells, opening up for a better understanding of the role of PDGF signaling during lung development.
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| 25. |
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| 26. |
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| 27. |
- Gustafsson, Per M., 1952, et al.
(författare)
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End-expiratory lung volume remains stable during N-2 MBW in healthy sleeping infants
- 2020
-
Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 8:16
-
Tidskriftsartikel (refereegranskat)abstract
- We have previously shown that functional residual capacity (FRC) and lung clearance index were significantly greater in sleeping healthy infants when measured by N-2 (nitrogen) washout using 100% O-2(oxygen) versus 4% SF6(sulfur hexafluoride) washout using air. Following 100% O-2 exposure, tidal volumes decreased by over 30%, while end-expiratory lung volume (EELV, i.e., FRC) rose markedly based on ultrasonic flow meter assessments. In the present study to investigate the mechanism behind the observed changes, N-2 MBW was performed in 10 separate healthy full-term spontaneously sleeping infants, mean (range) 26 (18-31) weeks, with simultaneous EELV monitoring (respiratory inductance plethysmography, RIP) and oxygen uptake (V ' O-2) assessment during prephase air breathing, during N-2 washout by exposure to 100% O-2, and subsequently during air breathing. While flow meter signals suggested a rise in ELLV by mean (SD) 26 (9) ml over the washout period, RIP signals demonstrated no EELV change. V'O-2/FRC ratio during air breathing was mean (SD) 0.43 (0.08)/min, approximately seven times higher than that calculated from adult data. We propose that our previously reported flow meter-based overestimation of EELV was in fact a physiological artifact caused by rapid and marked movement of O-2 across the alveolar capillary membrane into the blood and tissue during 100% O-2 exposure, without concomitant transfer of N(2)to the same degree in the opposite direction. This may be driven by the high observed O-2 consumption and resulting cardiac output encountered in infancy. Furthermore, the low resting lung volume in infancy may make this error in lung volume determination by N-2 washout relatively large.
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| 28. |
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| 29. |
- He, Rebecca S. S., et al.
(författare)
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Allometric scaling of metabolic rate and cardiorespiratory variables in aquatic and terrestrial mammals
- 2023
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Ingår i: Physiological Reports. - : WILEY. - 2051-817X. ; 11:11
-
Tidskriftsartikel (refereegranskat)abstract
- While basal metabolic rate (BMR) scales proportionally with body mass (M-b), it remains unclear whether the relationship differs between mammals from aquatic and terrestrial habitats. We hypothesized that differences in BMR allometry would be reflected in similar differences in scaling of O-2 delivery pathways through the cardiorespiratory system. We performed a comparative analysis of BMR across 63 mammalian species (20 aquatic, 43 terrestrial) with a M-b range from 10 kg to 5318 kg. Our results revealed elevated BMRs in small (>10 kg and <100 kg) aquatic mammals compared to small terrestrial mammals. The results demonstrated that minute ventilation, that is, tidal volume (V-T)center dot breathing frequency (f(R)), as well as cardiac output, that is, stroke volume center dot heart rate, do not differ between the two habitats. We found that the "aquatic breathing strategy", characterized by higher V-T and lower f(R) resulting in a more effective gas exchange, and by elevated blood hemoglobin concentrations resulting in a higher volume of O-2 for the same volume of blood, supported elevated metabolic requirements in aquatic mammals. The results from this study provide a possible explanation of how differences in gas exchange may serve energy demands in aquatic versus terrestrial mammals.
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| 30. |
- Holm, Lars, et al.
(författare)
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An exploration of the methods to determine the protein-specific synthesis and breakdown rates in vivo in humans.
- 2019
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Ingår i: Physiological Reports. - : John Wiley & Sons. - 2051-817X. ; 7:17
-
Tidskriftsartikel (refereegranskat)abstract
- The present study explores the methods to determine human in vivo protein-specific myofibrillar and collagenous connective tissue protein fractional synthesis and breakdown rates. We found that in human myofibrillar proteins, the protein-bound tracer disappearance method to determine the protein fractional breakdown rate (FBR) (via 2 H2 O ingestion, endogenous labeling of 2 H-alanine that is incorporated into proteins, and FBR quantified by its disappearance from these proteins) has a comparable intrasubject reproducibility (range: 0.09-53.5%) as the established direct-essential amino acid, here L-ring-13 C6 -phenylalanine, incorporation method to determine the muscle protein fractional synthesis rate (FSR) (range: 2.8-56.2%). Further, the determination of the protein breakdown in a protein structure with complex post-translational processing and maturation, exemplified by human tendon tissue, was not achieved in this experimentation, but more investigation is encouraged to reveal the possibility. Finally, we found that muscle protein FBR measured with an essential amino acid tracer prelabeling is inappropriate presumably because of significant and prolonged intracellular recycling, which also may become a significant limitation for determination of the myofibrillar FSR when repeated infusion trials are completed in the same participants.
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| 31. |
- Holmberg, Ellinor, 1975-, et al.
(författare)
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Allopregnanolone preferentially induces energy-rich food intake in male Wistar rats
- 2014
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Ingår i: Physiological Reports. - : Wiley Periodicals Inc.. - 2051-817X. ; 2:12, s. e12190-
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is an increasing problem and identification of the driving forces for overeating of energy-rich food is important. Previous studies show that the stress and sex steroid allopregnanolone has a hyperphagic effect on both bland food and palatable food. If allopregnanolone induces a preference for more palatable or for more energy-rich food is not known. The aim of this study was to elucidate the influence of allopregnanolone on food preference. Male Wistar rats were subjected to two different food preference tests: a choice between standard chow and cookies (which have a higher energy content and also are more palatable than chow), and a choice between a low caloric sucrose solution and standard chow (which has a higher energy content and is less palatable than sucrose). Food intake was measured for 1 h after acute subcutaneous injections of allopregnanolone. In the choice between cookies and chow allopregnanolone significantly increased only the intake of cookies.When the standard chow was the item present with the highest caloric load, the chow intake was increased and allopregnanolone had no effect on intake of the 10% sucrose solution. The increased energy intakes induced by the high allopregnanolone dose compared to vehicle were very similar in the two tests,120% increase for cookies and 150% increase for chow. It appears that in allopregnanolone-induced hyperphagia, rats choose the food with the highest energy content regardless of its palatability.
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| 32. |
- Hultström, Michael, 1978-, et al.
(författare)
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Surgical trauma is associated with renal immune cell activation in rats : A microarray study
- 2021
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Ingår i: Physiological Reports. - : John Wiley & Sons. - 2051-817X. ; 9:23
-
Tidskriftsartikel (refereegranskat)abstract
- Acute kidney injury (AKI) is a common perioperative complication that is associated with increased mortality. This study investigates the renal gene expression in male Long-Evans rats after prolonged anesthesia and surgery to detect molecular mechanisms that could predispose the kidneys to injury upon further insults. Healthy and streptozotocin diabetic rats that underwent autoregulatory investigation in an earlier study were compared to rats that were sacrificed quickly for mRNA quantification in the same study. Prolonged surgery caused massive changes in renal mRNA expression by microarray analysis, which was validated by quantitative real-time PCR with good correlation. Furthermore, bioinformatics analysis using gene ontology and pathway analysis identified biological processes involved in immune system activation, such as immune system processes (p = 1.3 x 10(-80)), immune response (p = 1.3 x 1(-60)), and regulation of cytokine production (p = 1.7 x 10(-52)). PCR analysis of specific cell type markers indicated that the gene activation in kidneys was most probably macrophages, while granulocytes and T cell appeared less activated. Immunohistochemistry was used to quantify immune cell infiltration and showed no difference between groups indicating that the genetic activation depends on the activation of resident cells, or infiltration of a relatively small number of highly activated cells. In follow-up experiments, surgery was performed on healthy rats under standard and sterile condition showing similar expression of immune cell markers, which suggests that the inflammation was indeed caused by the surgical trauma rather than by bacterial infection. In conclusion, surgical trauma is associated with rapid activation of immune cells, most likely macrophages in rat kidneys.
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| 33. |
- Iresjö, Britt-Marie, 1963, et al.
(författare)
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Food intake, tumor growth, and weight loss in EP2 receptor subtype knockout mice bearing PGE2-producing tumors
- 2015
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Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 3:7, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies in our laboratory have demonstrated that prostaglandin (PG) E2 is involved in anorexia/cachexia development in MCG 101 tumor‐bearing mice. In the present study, we investigate the role of PGE receptor subtype EP2 in the development of anorexia after MCG 101 implantation in wild‐type (EP2+/+) or EP2‐receptor knockout (EP2−/−) mice. Our results showed that host absence of EP2 receptors attenuated tumor growth and development of anorexia in tumor‐bearing EP2 knockout mice compared to tumor‐bearing wild‐type animals. Microarray profiling of the hypothalamus revealed a relative twofold change in expression of around 35 genes including mRNA transcripts coding for Phospholipase A2 and Prostaglandin D2 synthase (Ptgds) in EP2 receptor knockout mice compared to wild‐type mice. Prostaglandin D2 synthase levels were increased significantly in EP2 receptor knockouts, suggesting that improved food intake may depend on altered balance of prostaglandin production in hypothalamus since PGE2 and PGD2 display opposing effects in feeding control.
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| 34. |
- Iresjö, Britt-Marie, 1963, et al.
(författare)
-
Preoperative overnight parenteral nutrition (TPN) improves skeletal muscle protein metabolism indicated by microarray algorithm analyses in a randomized trial
- 2016
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Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 4:11
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Tidskriftsartikel (refereegranskat)abstract
- Loss of muscle mass is associated with increased risk of morbidity and mortality in hospitalized patients. Uncertainties of treatment efficiency by short-term artificial nutrition remain, specifically improvement of protein balance in skeletal muscles. In this study, algorithmic microarray analysis was applied to map cellular changes related to muscle protein metabolism in human skeletal muscle tissue during provision of overnight preoperative total parenteral nutrition (TPN). Twenty-two patients (11/group) scheduled for upper GI surgery due to malignant or benign disease received a continuous peripheral all-in-one TPN infusion (30 kcal/kg/day, 0.16 gN/kg/day) or saline infusion for 12 h prior operation. Biopsies from the rectus abdominis muscle were taken at the start of operation for isolation of muscle RNA. RNA expression microarray analyses were performed with Agilent Sureprint G3, 8 9 60K arrays using one-color labeling. 447 mRNAs were differently expressed between study and control patients (P < 0.1). mRNAs related to ribosomal biogenesis, mRNA processing, and translation were upregulated during overnight nutrition; particularly anabolic signaling S6K1 (P < 0.01-0.1). Transcripts of genes associated with lysosomal degradation showed consistently lower expression during TPN while mRNAs for ubiquitin-mediated degradation of proteins as well as transcripts related to intracellular signaling pathways, PI3 kinase/MAPkinase, were either increased or decreased. In conclusion, muscle mRNA alterations during overnight standard TPN infusions at constant rate altered mRNAs associated with mTOR signaling; increased initiation of protein translation; and suppressed autophagy/lysosomal degradation of proteins. This indicates that overnight preoperative parenteral nutrition is effective to promote muscle protein metabolism.
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| 35. |
- Jansson, Anna, et al.
(författare)
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Increased body fat content in horses alters metabolic and physiological exercise response, decreases performance, and increases locomotion asymmetry
- 2021
-
Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- This study examined the effect of altered body weight (BW) and body fat content on exercise performance and recovery. Nine horses were divided into two groups, and changes in BW and fat content were induced by feeding a high (HA) or restricted (RA) energy allowance for 36 days in a cross-over design. In the last week of each treatment, BW and body condition score (BCS) were recorded, body fat percentage was estimated using ultrasound, and a standardized incremental treadmill exercise test (SET) and competition-like field test were performed (scored by judges blinded to treatments). Blood samples were collected, and heart rate (HR), rectal temperature (RT), and respiratory rate (RR) were also recorded. Objective locomotion analyses were performed before and after the field test. Body weight, body fat percentage, and BCS were higher (5-8%) in HA than in RA horses (p < 0.05). In SET, HA horses showed higher HR, plasma lactate concentration, RR, and RT than RA horses (p < 0.05), and lower VLa4, hematocrit (Hct), plasma glucose, and plasma NEFA concentrations (p < 0.05). Hct was also lower in HA horses in the field test, while RA horses showed higher scores (p < 0.05). After both tests, resting plasma lactate concentrations were reached faster in RA than in HA horses (p < 0.05). Objective locomotion asymmetry was higher in HA than in RA (p < 0.05). These results clearly show that increased BW and body fat content in horses lower physiological fitness in terms of VLa4, plasma lactate removal, Hct levels, plasma glucose availability and reduce true performance evaluated by blinded judges.
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| 36. |
- Jensen, Line, et al.
(författare)
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Carbohydrate restricted recovery from long term endurance exercise does not affect gene responses involved in mitochondrial biogenesis in highly trained athletes
- 2015
-
Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 3:2
-
Tidskriftsartikel (refereegranskat)abstract
- The aim was to determine if the metabolic adaptations, particularly PGC-1a and downstream metabolic genes were affected by restricting CHO following an endurance exercise bout in trained endurance athletes. A second aim was to compare baseline expression level of these genes to untrained. Elite endurance athletes (VO2max 66 ± 2 mL·kg-1·min-1, n = 15) completed 4 h cycling at ~56% VO2max. During the first 4 h recovery subjects were provided with either CHO or only H2O and thereafter both groups received CHO. Muscle biopsies were collected before, after, and 4 and 24 h after exercise. Also, resting biopsies were collected from untrained subjects (n = 8). Exercise decreased glycogen by 67.7 ± 4.0% (from 699 ± 26.1 to 239 ± 29.5 mmol·kg-1·dw-1) with no difference between groups. Whereas 4 h of recovery with CHO partly replenished glycogen, the H2O group remained at post exercise level; nevertheless, the gene expression was not different between groups. Glycogen and most gene expression levels returned to baseline by 24 h in both CHO and H2O. Baseline mRNA expression of NRF-1, COX-IV, GLUT4 and PPAR-α gene targets were higher in trained compared to untrained. Additionally, the proportion of type I muscle fibers positively correlated with baseline mRNA for PGC-1α, TFAM, NRF-1, COX-IV, PPAR-α, and GLUT4 for both trained and untrained. CHO restriction during recovery from glycogen depleting exercise does not improve the mRNA response of markers of mitochondrial biogenesis. Further, baseline gene expression of key metabolic pathways is higher in trained than untrained.
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| 37. |
- Jäderkvist Fegraeus, Kim, et al.
(författare)
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A potential regulatory region near the EDN3 gene may control both harness racing performance and coat color variation in horses
- 2018
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Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 6:10
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Tidskriftsartikel (refereegranskat)abstract
- The Swedish‐Norwegian Coldblooded trotter and the heavier North‐Swedish draught horse both descend from the North‐Swedish horse, but the Coldblooded trotters have been selected for racing performance while the North‐Swedish draught horse is mainly used for agricultural and forestry work. By comparing the genomes of Coldblooded trotters, North‐Swedish draught horses and Standardbreds for a large number of single‐nucleotide polymorphisms (SNPs), the aim of the study was to identify genetic regions that may be under selection for racing performance. We hypothesized that the selection for racing performance, in combination with unauthorized crossbreeding of Coldblooded trotters and Standardbreds, has created regions in the genome where the Coldblooded trotters and Standardbreds are similar, but differ from the North‐Swedish draught horse. A fixation index (Fst) analysis was performed and sliding window Delta Fst values were calculated across the three breeds. Five windows, where the average Fst between Coldblooded trotters and Standardbreds was low and the average Fst between Coldblooded trotters and North‐Swedish draught horses was high, were selected for further investigation. Associations between the most highly ranked SNPs and harness racing performance were analyzed in 400 raced Coldblooded trotters with race records. One SNP showed a significant association with racing performance, with the CC genotype appearing to be negatively associated. The SNP identified was genotyped in 1915 horses of 18 different breeds. The frequency of the TT genotype was high in breeds typically used for racing and show jumping while the frequency of the CC genotype was high in most pony breeds and draught horses. The closest gene in this region was the Endothelin3 gene (EDN3), a gene mainly involved in melanocyte and enteric neuron development. Both functional genetic and physiological studies are needed to fully understand the possible impacts of the gene on racing performance.
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| 38. |
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| 39. |
- Keramidas, Michail E., et al.
(författare)
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PlanHab: Hypoxia counteracts the erythropoietin suppression, but seems to exaggerate the plasma volume reduction induced by 3 weeks of bed rest
- 2016
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Ingår i: Physiological Reports. - : Wiley-Blackwell. - 2051-817X. ; 4:3
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Tidskriftsartikel (refereegranskat)abstract
- The study examined the distinct and synergistic effects of hypoxia and bed rest on the erythropoietin (EPO) concentration and relative changes in plasma volume (PV). Eleven healthy male lowlanders underwent three 21‐day confinement periods, in a counterbalanced order: (1) normoxic bed rest (NBR; PIO2: 133.1 ± 0.3 mmHg); (2) hypoxic bed rest (HBR; PIO2: 90.0 ± 0.4 mmHg, ambient simulated altitude of ~4000 m); and (3) hypoxic ambulation (HAMB; PIO2: 90.0 ± 0.4 mmHg). Blood samples were collected before, during (days 2, 5, 14, and 21) and 2 days after each confinement to determine EPO concentration. Qualitative differences in PV changes were also estimated by changes in hematocrit and hemoglobin concentration along with concomitant changes in plasma renin concentration. NBR caused an initial reduction in EPO by ~39% (P = 0.04). By contrast, HBR enhanced EPO (P = 0.001), but the increase was less than that induced by HAMB (P < 0.01). All three confinements caused a significant reduction in PV (P < 0.05), with a substantially greater drop in HBR than in the other conditions (P < 0.001). Thus, present results suggest that hypoxia prevents the EPO suppression, whereas it seems to exaggerate the PV reduction induced by bed rest.
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| 40. |
- Kijani, Siavash, et al.
(författare)
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Intimal hyperplasia induced by vascular intervention causes lipoprotein retention and accelerated atherosclerosis
- 2017
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Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 5:14
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Tidskriftsartikel (refereegranskat)abstract
- Accelerated atherosclerosis diminishes the long term patency of vascular interventions, such as percutaneous coronary intervention and implantation of saphenous vein grafts. However, the cause of this accelerated atherosclerosis is unclear. In this study, we tested the hypothesis that intimal hyperplasia formed following vascular intervention promotes retention of atherogenic lipoproteins. Intimal hyperplasia was surgically induced in the mouse common carotid artery. The surgery was combined with different mouse models of hypercholesterolemia to obtain different cholesterol levels and to control the onsets of hypercholesterolemia. Three weeks after surgery, samples were immunostained for apoB lipoproteins, smooth muscle cells and leukocytes. Already at mild hypercholesterolemia (193mg/dL), pronounced apoB lipoprotein retention was found in the extracellular matrix in both intimal hyperplasia and the injured underlying media. In contrast, minimal retention was detected in the uninjured proximal region of the same vessel, or in vessels from mice with normal cholesterol levels (81mg/dL). Induction of aggravated hypercholesterolemia 3weeks after surgery, when a mature intimal hyperplasia had been formed, caused a very rapid development of atherosclerotic lesions. Mechanistically, we show that lipoprotein retention was almost exclusively dependent on electrostatic interactions to proteoglycan glycosaminoglycans, and the lipoprotein retention to intimal hyperplasia could be inhibited invivo using glycosaminoglycan-binding antibodies. Thus, formation of intimal hyperplasia following vascular intervention makes the vessel wall highly susceptible for lipoprotein retention and accelerated atherosclerosis. The increased lipoprotein retention in intimal hyperplasia can be targeted by blocking the interaction between apoB lipoproteins and glycosaminoglycans in the extracellular matrix.
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| 41. |
- Kjellberg, Sanna, et al.
(författare)
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Impaired function in the lung periphery following COVID-19 is associated with lingering breathing difficulties
- 2024
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Ingår i: PHYSIOLOGICAL REPORTS. - 2051-817X. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- Lingering breathing difficulties are common after COVID-19. However, the underlying causes remains unclear, with spirometry often being normal. We hypothesized that small airway dysfunction (SAD) can partly explain these symptoms. We examined 48 individuals (32 women, 4 hospitalized in the acute phase) who experienced dyspnea and/or cough in the acute phase and/or aftermath of COVID-19, and 22 non-COVID-19 controls. Time since acute infection was, median (range), 65 (10-131) weeks. We assessed SAD using multiple breath washout (MBW) and impulse oscillometry (IOS) and included spirometry and diffusing-capacity test (DLCO). One-minute-sit-to-stand test estimated physical function, and breathing difficulties were defined as answering "yes" to the question "do you experience lingering breathing difficulties?" Spirometry, DLCO, and IOS were normal in almost all cases (spirometry: 90%, DLCO: 98%, IOS: 88%), while MBW identified ventilation inhomogeneity in 50%. Breathing difficulties (n = 21) was associated with increased MBW-derived Sacin. However, physical function did not correlate with SAD. Among individuals with breathing difficulties, 25% had reduced physical function, 25% had SAD, 35% had both, and 15% had normal lung function and physical function. Despite spirometry and DLCO being normal in almost all post-COVID-19 individuals, SAD was present in a high proportion and was associated with lingering breathing difficulties.
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| 42. |
- Kristenson, Karolina, et al.
(författare)
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Peak oxygen uptake in combination with ventilatory efficiency improve risk stratification in major abdominal surgery
- 2024
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Ingår i: Physiological Reports. - : WILEY. - 2051-817X. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- This pilot study aimed to evaluate if peak VO2 and ventilatory efficiency in combination would improve preoperative risk stratification beyond only relying on peak VO2. This was a single-center retrospective cohort study including all patients who underwent cardiopulmonary exercise testing (CPET) as part of preoperative risk evaluation before major upper abdominal surgery during years 2008-2021. The primary outcome was any major cardiopulmonary complication during hospitalization. Forty-nine patients had a preoperative CPET before decision to pursue to surgery (cancer in esophagus [n = 18], stomach [6], pancreas [16], or liver [9]). Twenty-five were selected for operation. Patients who suffered any major cardiopulmonary complication had lower ventilatory efficiency (i.e., higher VE/VCO2 slope, 37.3 vs. 29.7, p = 0.031) compared to those without complications. In patients with a low aerobic capacity (i.e., peak VO2 < 20 mL/kg/min) and a VE/VCO2 slope >= 39, 80% developed a major cardiopulmonary complication. In this pilot study of patients with preoperative CPET before major upper abdominal surgery, patients who experienced a major cardiopulmonary complication had significantly lower ventilatory efficiency compared to those who did not. A low aerobic capacity in combination with low ventilatory efficiency was associated with a very high risk (80%) of having a major cardiopulmonary complication.
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| 43. |
- Krmar, Rafael T., et al.
(författare)
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Effect of controlled hypotensive hemorrhage on plasma sodium levels in anesthetized pigs : An exploratory study
- 2023
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Ingår i: Physiological Reports. - : John Wiley & Sons. - 2051-817X. ; 11:22
-
Tidskriftsartikel (refereegranskat)abstract
- Perioperative hyponatremia, due to non-osmotic release of the antidiuretic hormone arginine vasopressin, is a serious electrolyte disorder observed in connection with many types of surgery. Since blood loss during surgery contributes to the pathogenesis of hyponatremia, we explored the effect of bleeding on plasma sodium using a controlled hypotensive hemorrhage pig model. After 30-min baseline period, hemorrhage was induced by aspiration of blood during 30 min at mean arterial pressure <50 mmHg. Thereafter, the animals were resuscitated with retransfused blood and a near-isotonic balanced crystalloid solution and monitored for 180 min. Electrolyte and water balances, cardiovascular response, renal hemodynamics, and markers of volume regulation and osmoregulation were investigated. All pigs (n = 10) developed hyponatremia. All animals retained hypotonic fluid, and none could excrete net-free water. Urinary excretion of aquaporin 2, a surrogate marker of collecting duct responsiveness to antidiuretic hormone, was significantly reduced at the end of the study, whereas lysine vasopressin, i.e., the pig antidiuretic hormone remained high. In this animal model, hyponatremia developed due to net positive fluid balance and generation of electrolyte-free water by the kidneys. A decreased urinary aquaporin 2 excretion may indicate an escape from antidiuresis.
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| 44. |
- Larsen, Steen, et al.
(författare)
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Increased intrinsic mitochondrial respiratory capacity in skeletal muscle from rats with streptozotocin-induced hyperglycemia.
- 2015
-
Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 3:7
-
Tidskriftsartikel (refereegranskat)abstract
- Type I diabetes mellitus (T1DM) is a chronic disorder, characterized by an almost or complete insulin deficiency. Widespread tissue dysfunction and deleterious diabetes-complications are associated with long-term elevations of blood glucose. The aim of this study was to investigate the effects of type I diabetes, as induced by streptozotocin, on the mitochondria in skeletal muscles that predominantly consist of either slow or fast twitch fibers. Soleus (primarily slow twitch fiber type) and the plantaris muscle (mainly fast twitch fiber type) were removed in order to measure mitochondrial protein expression and integrated mitochondrial respiratory function. Mitochondrial capacity for oxidative phosphorylation (OXPHOS) was found to be higher in the slow (more oxidative) soleus muscle from STZ rats when evaluating lipid and complex I linked OXPHOS capacity, whereas no difference was detected between the groups when evaluating the more physiological complex I and II linked OXPHOS capacity. These findings indicate that chronic hyperglycemia results in an elevated intrinsic mitochondrial respiratory capacity in both soleus and, at varying degree, plantaris muscle, findings that are consistent with human T1DM patients.
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| 45. |
- Laustsen, Christoffer, et al.
(författare)
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Insufficient insulin administration to diabetic rats increases substrate utilization and maintains lactate production in the kidney
- 2014
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Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 2:12
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Tidskriftsartikel (refereegranskat)abstract
- Good glycemic control is crucial to prevent the onset and progression of late diabetic complications, but insulin treatment often fails to achieve normalization of glycemic control to the level seen in healthy controls. In fact, recent experimental studies indicate that insufficient treatment with insulin, resulting in poor glycemic control, has an additional effect on progression of late diabetic complications, than poor glycemic control on its own. We therefore compared renal metabolic alterations during conditions of poor glycemic control with and without suboptimal insulin administration, which did not restore glycemic control, to streptozotocin (STZ)-diabetic rats using noninvasive hyperpolarized (13)C-pyruvate magnetic resonance imaging (MRI) and blood oxygenation level-dependent (BOLD) (1)H-MRI to determine renal metabolic flux and oxygen availability, respectively. Suboptimal insulin administration increased pyruvate utilization and metabolic flux via both anaerobic and aerobic pathways in diabetic rats even though insulin did not affect kidney oxygen availability, HbA1c, or oxidative stress. These results imply direct effects of insulin in the regulation of cellular substrate utilization and metabolic fluxes during conditions of poor glycemic control. The study demonstrates that poor glycemic control in combination with suboptimal insulin administration accelerates metabolic alterations by increasing both anaerobic and aerobic metabolism resulting in increased utilization of energy substrates. The results demonstrate the importance of tight glycemic control in insulinopenic diabetes, and that insulin, when administered insufficiently, adds an additional burden on top of poor glycemic control.
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| 46. |
- Li, Hao, 1984-, et al.
(författare)
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Effects of Lactobacillus johnsonii and Lactobacillus reuteri on gut barrier function and heat shock proteins in intestinal porcine epithelial cells
- 2015
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Ingår i: Physiological Reports. - : WILEY. - 2051-817X. ; 3:4
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Tidskriftsartikel (refereegranskat)abstract
- Heat shock proteins (HSPs) are a set of highly conserved proteins that can serve as intestinal gate keepers in gut homeostasis. Here, effects of a probiotic, Lactobacillus rhamnosus GG (LGG), and two novel porcine isolates, Lactobacillus johnsonii strain P47-HY and Lactobacillus reuteri strain P43-HUV, on cyto-protective HSP expression and gut barrier function, were investigated in a porcine IPEC-J2 intestinal epithelial cell line model. The IPEC-J2 cells polarized on a permeable filter exhibited villus-like cell phenotype with development of apical microvilli. Western blot analysis detected HSP expression in IPEC-J2 and revealed that L. johnsonii and L. reuteri strains were able to significantly induce HSP27, despite high basal expression in IPEC-J2, whereas LGG did not. For HSP72, only the supernatant of L. reuteri induced the expression, which was comparable to the heat shock treatment, which indicated that HSP72 expression was more stimulus specific. The protective effect of lactobacilli was further studied in IPEC-J2 under an enterotoxigenic Escherichia coli (ETEC) challenge. ETEC caused intestinal barrier destruction, as reflected by loss of cell-cell contact, reduced IPEC-J2 cell viability and transepithelial electrical resistance, and disruption of tight junction protein zonula occludens-1. In contrast, the L. reuteri treatment substantially counteracted these detrimental effects and preserved the barrier function. L. johnsonii and LGG also achieved barrier protection, partly by directly inhibiting ETEC attachment. Together, the results indicate that specific strains of Lactobacillus can enhance gut barrier function through cytoprotective HSP induction and fortify the cell protection against ETEC challenge through tight junction protein modulation and direct interaction with pathogens.
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| 47. |
- Liljedahl, Leena, et al.
(författare)
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Effects of insulin and the glucagon-like peptide 1 receptor agonist liraglutide on the kidney proteome in db/db mice.
- 2017
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Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 5:6
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Tidskriftsartikel (refereegranskat)abstract
- Diabetes mellitus (DM) is a worldwide disease that affects 9% of the adult world population and type 2 DM accounts for 90% of those. A common consequence of DM is kidney complications, which could lead to kidney failure. We studied the potential effects of treatment with insulin and the glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide on the diabetic kidney proteome through the use of the db/db mouse model system and mass spectrometry (MS). Multivariate analyses revealed distinct effects of insulin and liraglutide on the db/db kidney proteome, which was seen on the protein levels of, for example, pterin-4 α-carbinolamine dehydratase/dimerization cofactor of hepatocyte nuclear factor-1α (PCBD1), neural precursor cell expressed developmentally down-regulated-8 (NEDD8), transcription elongation factor-B polypeptide-1 (ELOC) and hepcidin (HEPC). Furthermore, the separation of the insulin, liraglutide and vehicle db/db mouse groups in multivariate analyses was not mainly related to the albumin excretion rate (AER) or the level of glycated hemoglobin A1c (HbA1c%) in the mice. In summary, we show that insulin and liraglutide give rise to separate protein profiles in the db/db mouse kidney.
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| 48. |
- Liljedahl, Leena, et al.
(författare)
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The impact of the glucagon-like peptide 1 receptor agonist liraglutide on the streptozotocin-induced diabetic mouse kidney proteome
- 2019
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Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 7:4
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Tidskriftsartikel (refereegranskat)abstract
- In diabetes mellitus (DM), the kidneys are exposed to increased levels of hyperglycemia-induced oxidative stress. Elevated amounts of reactive oxygen species (ROS) are believed to provoke ultrastructural changes in kidney tissue and can eventually result in DM late complications such as diabetic nephropathy. While it is reported that glucagon-like peptide 1 receptors (GLP-1R) are present in the kidney vasculature, the effects of GLP-1 on the kidney proteome in DM is not well described. Thus, we set out to investigate potential effects on the proteomic level. Here the effects of GLP-1R agonism using the GLP-1 analogue liraglutide are studied in the kidneys of streptozotocin (STZ)-treated mice (n = 6/group) by label-free shotgun mass spectrometry (MS) and targeted MS. Unsupervised and supervised multivariate analyses are followed by one-way ANOVA. Shotgun MS data of vehicle and liraglutide-treated mouse groups are separated in the supervised multivariate analysis and separation is also achieved in the subsequent unsupervised multivariate analysis using targeted MS data. The mouse group receiving the GLP-1R agonist liraglutide has increased protein abundances of glutathione peroxidase-3 (GPX3) and catalase (CATA) while the abundances of neuroplastin (NPTN) and bifunctional glutamate/proline–tRNA ligase (SYEP) are decreased compared to the STZ vehicle mice. The data suggest that GLP-1R agonism mainly influences abundances of structurally involved proteins and proteins involved in oxidative stress responses in the STZ mouse kidney. The changes could be direct effects of GLP-1R agonism in the kidneys or indirectly caused by a systemic response to GLP-1R activation.
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| 49. |
- Lubbad, Loay, et al.
(författare)
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Reduced glomerular size selectivity in late streptozotocin-induced diabetes in rats: application of a distributed two-pore model.
- 2015
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Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 3:5
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Tidskriftsartikel (refereegranskat)abstract
- Microalbuminuria is an early manifestation of diabetic nephropathy. Potential contributors to this condition are reduced glomerular filtration barrier (GFB) size- and charge selectivity, and impaired tubular reabsorption of filtered proteins. However, it was recently reported that no significant alterations in charge selectivity of the GFB occur in early experimental diabetic nephropathy. We here aimed at investigating the functional changes in the GFB in long-term type-1 diabetes in rats, applying a novel distributed two-pore model. We examined glomerular permeability in 15 male Wistar rats with at least 3 months of streptozotocin (STZ)-induced diabetes (blood glucose ∼20 mmol/L) and in age-matched control rats. The changes in glomerular permeability were assessed by determining the glomerular sieving coefficients (θ) for FITC-Ficoll (molecular radius 20-90 Å) using size exclusion HPLC. The values of θ for FITC-Ficoll of radius >50 Å were significantly increased in STZ-diabetic rats compared to age-matched controls (θ for 50-69 Å = 0.001 vs. 0.0002, and θ for 70-90 Å = 0.0007 vs. 0.00006, P < 0.001), while θ for FITC-Ficoll <50 Å tended to be lower in diabetic rats than in controls (θ for 36-49 Å = 0.013 vs. 0.016, ns). According to the distributed two-pore model, there was primarily an increase in macromolecular transport through large pores in the glomerular filter of diabetic rats associated with a loss of small-pore area. Deterioration in the glomerular size selectivity due to an increase in the number and size-spread of large pores, with no changes in the permeability of the small-pore system, represent the major functional changes observed after 3 months of induced experimental diabetes.
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| 50. |
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