| 1. |
- Abegg, K., et al.
(författare)
-
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
-
Ingår i: American Journal of Physiology-Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 308:4
-
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.
|
|
| 2. |
- Anesten, Fredrik, et al.
(författare)
-
Preproglucagon neurons in the hindbrain have IL-6 receptor-α and show Ca2+ influx in response to IL-6
- 2016
-
Ingår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 311:1
-
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.
|
|
| 3. |
- Astrand, Annika, et al.
(författare)
-
Mice lacking melanin-concentrating hormone receptor 1 demonstrate increased heart rate associated with altered autonomic activity.
- 2004
-
Ingår i: American journal of physiology. Regulatory, integrative and comparative physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 287:4
-
Tidskriftsartikel (refereegranskat)abstract
- Melanin-concentrating hormone (MCH) plays an important role in energy balance. The current studies were carried out on a new line of mice lacking the rodent MCH receptor (MCHR1(-/-) mice). These mice confirmed the previously reported lean phenotype characterized by increased energy expenditure and modestly increased caloric intake. Because MCH is expressed in the lateral hypothalamic area, which also has an important role in the regulation of the autonomic nervous system, heart rate and blood pressure were measured by a telemetric method to investigate whether the increased energy expenditure in these mice might be due to altered autonomic nervous system activity. Male MCHR1(-/-) mice demonstrated a significantly increased heart rate [24-h period: wild type 495 +/- 4 vs. MCHR1(-/-) 561 +/- 8 beats/min (P < 0.001); dark phase: wild type 506 +/- 8 vs. MCHR1(-/-) 582 +/- 9 beats/min (P < 0.001); light phase: wild type 484 +/- 13 vs. MCHR1(-/-) 539 +/- 9 beats/min (P < 0.005)] with no significant difference in mean arterial pressure [wild type 110 +/- 0.3 vs. MCHR1(-/-) 113 +/- 0.4 mmHg (P > 0.05)]. Locomotor activity and core body temperature were higher in the MCHR1(-/-) mice during the dark phase only and thus temporally dissociated from heart rate differences. On fasting, wild-type animals rapidly downregulated body temperature and heart rate. MCHR1(-/-) mice displayed a distinct delay in the onset of this downregulation. To investigate the mechanism underlying these differences, autonomic blockade experiments were carried out. Administration of the adrenergic antagonist metoprolol completely reversed the tachycardia seen in MCHR1(-/-) mice, suggesting an increased sympathetic tone.
|
|
| 4. |
- Bonne, T. C., et al.
(författare)
-
Phlebotomy eliminates the maximal cardiac output response to six weeks of exercise training
- 2014
-
Ingår i: American Journal of Physiology-Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 306:10
-
Tidskriftsartikel (refereegranskat)abstract
- With this study we tested the hypothesis that 6 wk of endurance training increases maximal cardiac output (Q(max)) relatively more by elevating blood volume (BV) than by inducing structural and functional changes within the heart. Nine healthy but untrained volunteers (Vo(2max) 47 +/- 5 ml.min(-1).kg(-1)) underwent supervised training (60 min; 4 times weekly at 65% Vo(2max) for 6 wk), and Q(max) was determined by inert gas rebreathing during cycle ergometer exercise before and after the training period. After the training period, blood volume (determined in duplicates by CO rebreathing) was reestablished to pretraining values by phlebotomy and Q(max) was quantified again. Resting echography revealed no structural heart adaptations as a consequence of the training intervention. After the training period, plasma volume (PV), red blood cell volume (RBCV), and BV increased (P < 0.05) by 147 +/- 168 (5 +/- 5%), 235 +/- 64 (10 +/- 3%), and 382 +/- 204 ml (7 +/- 4%), respectively. Vo(2max) was augmented (P < 0.05) by 10 +/- 7% after the training period and decreased (P < 0.05) by 8 +/- 7% with phlebotomy. Concomitantly, Q(max) was increased (P < 0.05) from 18.9 +/- 2.1 to 20.4 +/- 2.3 l/min (9 +/- 6%) as a consequence of the training intervention, and after normalization of BV by phlebotomy Q(max) returned to pretraining values (18.1 +/- 2.5 l/min; 12 +/- 5% reversal). Thus the exercise training-induced increase in BV is the main mechanism increasing Q(max) after 6 wk of endurance training in previously untrained subjects.
|
|
| 5. |
- Brijs, Jeroen, et al.
(författare)
-
Cardiac remodeling and increased central venous pressure underlie elevated stroke volume and cardiac output of seawater-acclimated rainbow trout
- 2017
-
Ingår i: American Journal of Physiology - Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 312:1
-
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.
|
|
| 6. |
- Brijs, Jeroen, et al.
(författare)
-
Cardiorespiratory upregulation during seawater acclimation in rainbow trout: effects on gastrointestinal perfusion and postprandial responses
- 2016
-
Ingår i: American Journal of Physiology-Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 310:9
-
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.
|
|
| 7. |
- Chapman, C. L., et al.
(författare)
-
Occupational heat exposure and the risk of chronic kidney disease of nontraditional origin in the United States
- 2021
-
Ingår i: American Journal of Physiology-Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 321:2
-
Tidskriftsartikel (refereegranskat)abstract
- Occupational heat exposure is linked to the development of kidney injury and disease in individuals who frequently perform physically demanding work in the heat. For instance, in Central America, an epidemic of chronic kidney disease of nontraditional origin (CKDnt) is occurring among manual laborers, whereas potentially related epidemics have emerged in India and Sri Lanka. There is growing concern that workers in the United States suffer with CKDnt, but reports are limited. One of the leading hypotheses is that repetitive kidney injury caused by physical work in the heat can progress to CKDnt. Whether heat stress is the primary causal agent or accelerates existing underlying pathology remains contested. However, the current evidence supports that heat stress induces tubular kidney injury, which is worsened by higher core temperatures, dehydration, longer work durations, muscle damaging exercise, and consumption of beverages containing high levels of fructose. The purpose of this narrative review is to identify occupations that may place US workers at greater risk of kidney injury and CKDnt. Specifically, we reviewed the scientific literature to characterize the demographics, environmental conditions, physiological strain (i.e., core temperature increase, dehydration, heart rate), and work durations in sectors typically experiencing occupational heat exposure, including farming, wildland firefighting, landscaping, and utilities. Overall, the surprisingly limited available evidence characterizing occupational heat exposure in US workers supports the need for future investigations to understand this risk of CKDnt.
|
|
| 8. |
- Charkoudian, N, et al.
(författare)
-
Integrative mechanisms of blood pressure regulation in humans and rats: cross-species similarities.
- 2010
-
Ingår i: American journal of physiology. Regulatory, integrative and comparative physiology. - : American Physiological Society. - 1522-1490 .- 0363-6119. ; 298:3
-
Tidskriftsartikel (refereegranskat)abstract
- As our understanding of the importance of individualized medicine continues to grow, the clinical relevance of interindividual variability in hemodynamic variables is receiving increasing attention. However, it is not known whether the rat, which is often used for studies of cardiovascular regulation, exhibits similar interindividual variability. In the present study, we evaluated whether the magnitude of interindividual variability in cardiac output (CO) and total peripheral resistance (TPR) was similar in humans and in rats. We assessed interindividual variability of mean arterial pressure (MAP), CO, and TPR during control conditions in normotensive humans (n = 40) and during normotension and deoxycorticosterone acetate-salt hypertension in Sprague-Dawley rats (n = 16). Humans and rats showed marked interindividual variability in CO and TPR but low variability in MAP. During deoxycorticosterone acetate-salt hypertension, CO was maintained, but TPR was elevated compared with the baseline period. We conclude that the magnitudes of interindividual variability of MAP, CO, and TPR are quantitatively similar in humans and rats, providing support for the relevance of this variability in both species and suggesting that studies in rats could be designed to address questions specific to individualized medicine in hypertension.
|
|
| 9. |
- Clark, T.D., et al.
(författare)
-
Circulatory limits to oxygen supply during an acute temperature increase in the Chinook salmon (Oncorhynchus tshawytscha)
- 2008
-
Ingår i: American Journal of Physiology: Regulatory, Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 295
-
Tidskriftsartikel (refereegranskat)abstract
- This study was undertaken to provide a comprehensive set of data relevant to disclosing the physiological effects and possible oxygen transport limitations in the Chinook salmon (Oncorhynchus tshawytscha) during an acute temperature change. Fish were instrumented with a blood flow probe around the ventral aorta and catheters in the dorsal aorta and sinus venosus. Water temperature was progressively increased from 13°C in steps of 4°C up to 25°C. Cardiac output increased from 29 to 56 ml·min–1·kg–1 between 13 and 25°C through an increase in heart rate (58 to 105 beats/min). Systemic vascular resistance was reduced, causing a stable dorsal aortic blood pressure, yet central venous blood pressure increased significantly at 25°C. Oxygen consumption rate increased from 3.4 to 8.7 mg·min–1·kg–1 during the temperature increase, although there were signs of anaerobic respiration at 25°C in the form of increased blood lactate and decreased pH. Arterial oxygen partial pressure was maintained during the heat stress, although venous oxygen partial pressure (PvO2) and venous oxygen content were significantly reduced. Cardiac arrhythmias were prominent in three of the largest fish (>4 kg) at 25°C. Given the switch to anaerobic metabolism and the observation of cardiac arrhythmias at 25°C, we propose that the cascade of venous oxygen depletion results in a threshold value for PvO2 of around 1 kPa. At this point, the oxygen supply to systemic and cardiac tissues is compromised, such that the oxygen-deprived and acidotic myocardium becomes arrhythmic, and blood perfusion through the gills and to the tissues becomes compromised.
|
|
| 10. |
- Edsbagge, Mikael, et al.
(författare)
-
Spinal CSF absorption in healthy individuals.
- 2004
-
Ingår i: American journal of physiology. Regulatory, integrative and comparative physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 287:6
-
Tidskriftsartikel (refereegranskat)abstract
- The present study examines the extent of spinal cerebrospinal fluid (CSF) absorption in healthy individuals in relation to physical activity, CSF production, intracranial pressure (ICP), and spinal CSF movement. Thirty-four healthy individuals aged 21-35 yr were examined by lumbar puncture and radionuclide cisternography with repeated imaging. ICP was registered before and after CSF drainage, and CSF production was calculated. Spinal CSF absorption was calculated as reduction in spinal radionuclide activity. The radionuclide activity in the spinal subarachnoidal space was gradually decreased by 20 +/- 13% (mean +/- SD) during 1 h. The reduction was higher in active than in resting individuals (27 +/- 12% vs. 13 +/- 9%). The mean ICP in 19 of the individuals was 13.6 +/- 3.1 cm H(2)O. B-waves were found in 79% of the individuals, with a mean frequency of 0.6 +/- 0.3 min(-1). The mean CSF production rate was 0.34 +/- 0.13 ml/min. There were no correlations between radionuclide reduction, spinal movement of the radionuclide, and CSF production rate. The spinal radionuclide reduction found in this study indicates a spinal CSF absorption of 0.11-0.23 ml/min, more pronounced in active than in resting individuals.
|
|
