| 1. |
- Abegg, K., et al.
(författare)
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Effect of bariatric surgery combined with medical therapy versus intensive medical therapy or calorie restriction and weight loss on glycemic control in Zucker diabetic fatty rats
- 2015
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Ingår i: American Journal of Physiology-Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 308:4
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Tidskriftsartikel (refereegranskat)abstract
- Bariatric surgery rapidly improves Type 2 diabetes mellitus (T2DM). Our objective was to profile and compare the extent and duration of improved glycemic control following Roux-en-Y gastric (RYGB) bypass surgery and vertical sleeve gastrectomy (SG) and compare against calorie restriction/weight loss and medical combination therapy-based approaches using the Zucker diabetic fatty rat (ZDF) rodent model of advanced T2DM. Male ZDF rats underwent RYGB (n = 15) or SG surgery (n = 10) at 18 wk of age and received postsurgical insulin treatment, as required to maintain mid-light-phase glycemia within a predefined range (10-15 mmol/l). In parallel, other groups of animals underwent sham surgery with ad libitum feeding (n = 6), with body weight (n = 8), or glycemic matching (n = 8) to the RYGB group, using food restriction or a combination of insulin, metformin, and liraglutide, respectively. Both bariatric procedures decreased the daily insulin dose required to maintain mid-light-phase blood glucose levels below 15 mmol/l, compared with those required by body weight or glycemia-matched rats (P < 0.001). No difference was noted between RYGB and SG with regard to initial efficacy. SG was, however, associated with higher food intake, weight regain, and higher insulin requirements vs. RYGB at study end (P < 0.05). Severe hypoglycemia occurred in several rats after RYGB. RYGB and SG significantly improved glycemic control in a rodent model of advanced T2DM. While short-term outcomes are similar, long-term efficacy appears marginally better after RYGB, although this is tempered by the increased risk of hypoglycemia.
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| 2. |
- Anesten, Fredrik, et al.
(författare)
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Preproglucagon neurons in the hindbrain have IL-6 receptor-α and show Ca2+ influx in response to IL-6
- 2016
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Ingår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 311:1
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Tidskriftsartikel (refereegranskat)abstract
- Neuronal circuits in the hypothalamus and hindbrain are of importance for control of food intake, energy expenditure, and fat mass. We have recently shown that treatment with exendin-4 (Ex-4), an analog of the proglucagonderived molecule glucagon-like peptide 1 (GLP-1), markedly increases mRNA expression of the cytokine interleukin-6 (IL-6) in the hypothalamus and hindbrain and that this increase partly mediates the suppression of food intake and body weight by Ex-4. Endogenous GLP-1 in the central nervous system (CNS) is produced by preproglucagon (PPG) neurons of the nucleus of the solitary tract (NTS) in the hindbrain. These neurons project to various parts of the brain, including the hypothalamus. Outside the brain, IL-6 stimulates GLP-1 secretion from the gut and pancreas. In this study, we aim to investigate whether IL-6 can affect GLP-1-producing PPG neurons in the nucleus of the solitary tract (NTS) in mouse hindbrain via the ligand binding part of the IL-6 receptor, IL-6 receptor-α (IL-6Rα). Using immunohistochemistry, we found that IL-6Rα was localized on PPG neurons of the NTS. Recordings of these neurons in GCaMP3/GLP-1 reporter mice showed that IL-6 enhances cytosolic Ca2+ concentration in neurons capable of expressing PPG. We also show that the Ca2+ increase originates from the extracellular space. Furthermore, we found that IL-6Rα was localized on cells in the caudal hindbrain expressing immunoreactive NeuN (a neuronal marker) or CNP:ase (an oligodendrocyte marker). In summary, IL-6Rα is present on PPG neurons in the NTS, and IL-6 can stimulate these cells by increasing influx of Ca2+ to the cytosol from the extracellular space. © 2016 the American Physiological Society.
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| 3. |
- Arvedsen, SK, et al.
(författare)
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Body height and arterial pressure in seated and supine young males during +2 G centrifugation
- 2015
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Ingår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 309:9
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Tidskriftsartikel (refereegranskat)abstract
- It is known that arterial pressure correlates positively with body height in males and it has been suggested that this is due to the increasing vertical hydrostatic gradient from the heart to the carotid baroreceptors. Therefore we tested the hypothesis that a higher gravitoinertial stress induced by the use of a human centrifuge would increase mean arterial pressure (MAP) more in tall than in short males in the seated position. In short (162-171cm, n=8) and tall (194-203cm, n=10) healthy males (18-41y), brachial arterial pressure, heart rate (HR) and cardiac output were measured during +2G centrifugation, while they were seated upright with the legs kept horizontal (+2Gz). In a separate experiment, the same measurements were done with the subjects supine (+2Gx). During +2Gz MAP increased in the short (22±2 mmHg, p<0.0001) and tall (23±2 mmHg, p<0.0001) males, with no significant difference between the groups. HR increased more (p<0.05) in the tall than in the short group (14±2 versus 7±2 bpm). Stroke volume (SV) decreased in the short group (26±4 mL, p=0.001) and more so in the tall group (39±5 mL, p<0.0001; short vs tall p=0.047). During +2GX, systolic arterial pressure increased (p<0.001) and SV (p=0.012) decreased in the tall group only. In conclusion, during +2Gz MAP increased in both short and tall males with no difference between the groups. However, in the tall group HR increased more during +2Gz which could be caused by a larger hydrostatic pressure gradient from heart to head leading to greater inhibition of the carotid baroreceptors.
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| 4. |
- Becirovic-Agic, Mediha, et al.
(författare)
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Time course of decompensation after angiotensin II and high-salt diet in Balb/CJ mice suggests pulmonary hypertension-induced cardiorenal syndrome
- 2019
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Ingår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology. - : the American Physiological Society. - 0363-6119 .- 1522-1490. ; 316:5, s. R563-R570
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Tidskriftsartikel (refereegranskat)abstract
- The genetic background of a mouse strain determines its susceptibility to disease. C57BL/6J and Balb/CJ are two widely used inbred mouse strains that we found react dramatically differently to angiotensin II and high-salt diet (ANG II + Salt). Balb/CJ show increased mortality associated with anuria and edema formation while C57BL/6J develop arterial hypertension but do not decompensate and die. Clinical symptoms of heart failure in Balb/CJ mice gave the hypothesis that ANG II + Salt impairs cardiac function and induces cardiac remodeling in male Balb/CJ but not in male C57BL/6J mice. To test this hypothesis, we measured cardiac function using echocardiography before treatment and every day for 7 days during treatment with ANG II + Salt. Interestingly, pulsed wave Doppler of pulmonary artery flow indicated increased pulmonary vascular resistance and right ventricle systolic pressure in Balb/CJ mice, already 24 h after ANG II + Salt treatment was started. In addition, Balb/CJ mice showed abnormal diastolic filling indicated by reduced early and late filling and increased isovolumic relaxation time. Furthermore, Balb/CJ exhibited lower cardiac output compared with C57BL/6J even though they retained more sodium and water, as assessed using metabolic cages. Left posterior wall thickness increased during ANG II + Salt treatment but did not differ between the strains. In conclusion, ANG II + Salt treatment causes early restriction of pulmonary flow and reduced left ventricular filling and cardiac output in Balb/CJ, which results in fluid retention and peripheral edema. This makes Balb/CJ a potential model to study the adaptive capacity of the heart for identifying new disease mechanisms and drug targets.
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| 5. |
- Bower, Rebekah L., et al.
(författare)
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Mapping the calcitonin receptor in human brain stem
- 2016
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Ingår i: American Journal of Physiology - Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 310:9, s. 788-793
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Tidskriftsartikel (refereegranskat)abstract
- The calcitonin receptor (CTR) is relevant to three hormonal systems: amylin, calcitonin, and calcitonin gene-related peptide (CGRP). Receptors for amylin and calcitonin are targets for treating obesity, diabetes, and bone disorders. CGRP receptors represent a target for pain and migraine. Amylin receptors (AMY) are a heterodimer formed by the coexpression of CTR with receptor activity-modifying proteins (RAMPs). CTR with RAMP1 responds potently to both amylin and CGRP. The brain stem is a major site of action for circulating amylin and is a rich site of CGRP binding. This study aimed to enhance our understanding of these hormone systems by mapping CTR expression in the human brain stem, specifically the medulla oblongata. Widespread CTR-like immunoreactivity was observed throughout the medulla. Dense CTR staining was noted in several discrete nuclei, including the nucleus of the solitary tract, the hypoglossal nucleus, the cuneate nucleus, spinal trigeminal nucleus, the gracile nucleus, and the inferior olivary nucleus. CTR staining was also observed in the area postrema, the lateral reticular nucleus, and the pyramidal tract. The extensive expression of CTR in the medulla suggests that CTR may be involved in a wider range of functions than currently appreciated.
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| 6. |
- Brijs, Jeroen, et al.
(författare)
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Cardiac remodeling and increased central venous pressure underlie elevated stroke volume and cardiac output of seawater-acclimated rainbow trout
- 2017
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Ingår i: American Journal of Physiology - Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 312:1
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Tidskriftsartikel (refereegranskat)abstract
- © 2017 the American Physiological Society.Substantial increases in cardiac output (CO), stroke volume (SV), and gastrointestinal blood flow are essential for euryhaline rainbow trout (Oncorhyncus mykiss) osmoregulation in seawater. However, the underlying hemodynamic mechanisms responsible for these changes are unknown. By examining a range of circulatory and cardiac morphological variables of seawater-and freshwater-acclimated rainbow trout, the present study revealed a significantly higher central venous pressure (CVP) in seawater-acclimated trout (~0.09 vs. -0.02 kPa). This serves to increase cardiac end-diastolic volume in seawater and explains the elevations in SV (~0.41 vs. 0.27 ml/kg) and CO (~21.5 vs. 14.2 ml·min-1·kg-1) when compared with trout in freshwater. Furthermore, these hemodynamic modifications coincided with a significant increase in the proportion of compact myocardium, which may be necessary to compensate for the increased wall tension associated with a larger stroke volume. Following a temperature increase from 10 to 16.5°C, both acclimation groups exhibited similar increases in heart rate (Q10 of ~2), but SV tended to decrease in seawater-acclimated trout despite the fact that CVP was maintained in both groups. This resulted in CO of seawaterand freshwater-acclimated trout stabilizing at a similar level after warming (~26 ml·min-1·kg-1). The consistently higher CVP of seawater-acclimated trout suggests that factors other than compromised cardiac filling constrained the SV and CO of these individuals at high temperatures. The present study highlights, for the first time, the complex interacting effects of temperature and water salinity on cardiovascular responses in a euryhaline fish species.
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| 7. |
- Brijs, Jeroen, et al.
(författare)
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Cardiorespiratory upregulation during seawater acclimation in rainbow trout: effects on gastrointestinal perfusion and postprandial responses
- 2016
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Ingår i: American Journal of Physiology-Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 310:9
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Tidskriftsartikel (refereegranskat)abstract
- Increased gastrointestinal blood flow is essential for euryhaline fishes to maintain osmotic homeostasis during the initial phase of a transition from freshwater to seawater. However, the cardiorespiratory responses and hemodynamic changes required for a successful long-term transition to seawater remain largely unknown. In the present study, we simultaneously measured oxygen consumption rate ((M)over dot(O2)), cardiac output (CO), heart rate (HR), and gastrointestinal blood flow (GBF) in rainbow trout (Oncorhynchus mykiss) acclimated to either freshwater or seawater for at least 6 wk. Seawater-acclimated trout displayed significantly elevated ((M)over dot(O2)) (day: 18%, night: 19%), CO (day: 22%, night: 48%), and GBF (day: 96%, night: 147%), demonstrating that an overall cardiorespiratory upregulation occurs during seawater acclimation. The elevated GBF was achieved via a combination of increased CO, mediated through elevated stroke volume (SV), and a redistribution of blood flow to the gastrointestinal tract. Interestingly, virtually all of the increase in CO of seawater-acclimated trout was directed to the gastrointestinal tract. Although unfed seawater-acclimated trout displayed substantially elevated cardiorespiratory activity, the ingestion of a meal resulted in a similar specific dynamic action (SDA) and postprandial GBF response as in freshwater-acclimated fish. This indicates that the capacity for the transportation of absorbed nutrients, gastrointestinal tissue oxygen delivery, and acid-base regulation is maintained during digestion in seawater. The novel findings presented in this study clearly demonstrate that euryhaline fish upregulate cardiovascular function when in seawater, while retaining sufficient capacity for the metabolic and cardiovascular changes associated with the postprandial response.
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| 8. |
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| 9. |
- Ekström, Andreas, 1979, et al.
(författare)
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Cardiac oxygen limitation during an acute thermal challenge in the European perch: Effects of chronic environmental warming and experimental hyperoxia
- 2016
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Ingår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 311:2
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Tidskriftsartikel (refereegranskat)abstract
- Oxygen supply to the heart has been hypothesized to limit cardiac performance and whole animal acute thermal tolerance (CTmax) in fish. We tested these hypotheses by continuously measuring venous oxygen tension (PvO2) and cardiovascular variables in vivo during acute warming in European perch (Perca fluviatilis) from a reference area during summer (18°C) and a chronically heated area (Biotest enclosure) that receives warm effluent water from a nuclear power plant and is normally 5–10°C above ambient (24°C at the time of experiments). While CTmax was 2.2°C higher in Biotest compared with reference perch, the peaks in cardiac output and heart rate prior to CTmax occurred at statistically similar PvO2 values (2.3– 4.0 kPa), suggesting that cardiac failure occurred at a common critical PvO2 threshold. Environmental hyperoxia (200% air saturation) increased PvO2 across temperatures in reference fish, but heart rate still declined at a similar temperature. CTmax of reference fish increased slightly (by 0.9°C) in hyperoxia, but remained significantly lower than in Biotest fish despite an improved cardiac output due to an elevated stroke volume. Thus, while cardiac oxygen supply appears critical to elevate stroke volume at high temperatures, oxygen limitation may not explain the bradycardia and arrhythmia that occur prior to CTmax. Acute thermal tolerance and its thermal plasticity can, therefore, only be partially attributed to cardiac failure from myocardial oxygen limitations, and likely involves limiting factors on multiple organizational levels. © 2016 the American Physiological Society.
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| 10. |
- Ekström, Andreas, 1979, et al.
(författare)
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Influence of the coronary circulation on thermal tolerance and cardiac performance during warming in rainbow trout
- 2017
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Ingår i: American Journal of Physiology - Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 312:4
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Tidskriftsartikel (refereegranskat)abstract
- © 2017 the American Physiological Society. Thermal tolerance in fish may be related to an oxygen limitation of cardiac function. While the hearts of some fish species receive oxygenated blood via a coronary circulation, the influence of this oxygen supply on thermal tolerance and cardiac performance during warming remain unexplored. Here, we analyzed the effect in vivo of acute warming on coronary blood flow in adult sexually mature rainbow trout (Onchorhynchus mykiss) and the consequences of chronic coronary ligation on cardiac function and thermal tolerance in juvenile trout. Coronary blood flow at 10°C was higher in females than males (0.56 ± 0.08 vs. 0.30 ± 0.08 ml·min -1 ·g ventricle -1 ), and averaged 0.47 ± 0.07 ml·min -1 ·g ventricle -1 across sexes. Warming increased coronary flow in both sexes until 14°C, at which it peaked and plateaued at 0.78 ± 0.1 and 0.61 ± 0.1 ml·min -1 ·g ventricle -1 in females and males, respectively. Thus, the scope for increasing coronary flow was 101% in males, but only 39% in females. Coronary-ligated juvenile trout exhibited elevated heart rate across temperatures, reduced Arrhenius breakpoint temperature for heart rate (23.0 vs. 24.6°C), and reduced upper critical thermal maximum (25.3 vs. 26.3°C). To further analyze the effects of coronary flow restriction on cardiac rhythmicity, electrocardiogram characteristics were determined before and after coronary occlusion in anesthetized trout. Occlusion resulted in reduced R-wave amplitude and an elevated S-T segment, indicating myocardial ischemia, while heart rate was unaffected. This suggests that the tachy cardia in ligated trout across temperatures in vivo was mainly to compensate for reduced cardiac contractility to maintain cardiac output. Moreover, our findings show that coronary flow increases with warming in a sex-specific manner. This may improve whole animal thermal tolerance, presumably by sustaining cardiac oxygenation and contractility at high temperatures.
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