Effect of Exercise on Pancreatic Islets in Zucker Diabetic Fatty Rats (original) (raw)
Biochemical and Biophysical Research Communications, 2013
We evaluated the effect of chronic exercise on insulin secretion in response to high-glucose by using a perifusion method with isolated pancreatic islets from normal rats. Male Wistar rats were assigned to one of two groups: a sedentary group and a trained group. Running exercise was carried out on a treadmill for one hour per day, five days per week, for six, nine, or 12 weeks. The chronic exercise significantly enhanced the insulin secretion ability of pancreatic islets in response to the high-glucose stimulation upon nine and 12 weeks of exercise. The insulin content in the pancreas and the weight of the pancreas did not change upon nine weeks of exercise. Potassium-stimulated insulin secretion was also increased in the islets isolated from rats that trained for nine weeks compared with that in sedentary rats, suggesting that insulin secretion events downstream of membrane depolarization are involved in targets of the exercise effect. These findings suggest that chronic exercise could be a useful strategy not only for the maintenance of peripheral insulin sensitivity but also for the promotion of islet function to secrete insulin in non-diabetics.
Cellular Physiology and Biochemistry, 2013
Background/Aims: Metabolic syndrome has been identified as one of the most significant threats to human health in the 21 st century. Exercise training has been shown to counteract obesity and metabolic syndrome. The present study aimed to investigate the effects of moderate exercise training on pancreatic beta-cell function and autonomic nervous system (ANS) activity in rats fed a high-fat diet (HFD). Methods: Weaning rats were divided into four groups: rats fed a standard chow or HFD (sedentary, Control-SED and HFD-SED; or exercised, Control-EXE and HFD-EXE, respectively). Exercised rats ran (from 21-to 91-daysold) for 60 minutes (3 times/week) over a 10-week period. Glucose and insulin tolerance tests were performed. Pancreatic islets were isolated to study glucose-induced insulin secretion (GIIS). Parasympathetic and sympathetic nerve electrical signals were measured, and liver samples were processed and histologically analyzed. Results: Exercise prevented obesity, insulin resistance, and liver steatosis as well as improved total cholesterol, ALT, and AST levels. Islets from HFD rats showed insulin hypersecretion which was ameliorated by exercise. Exercise decreased vagal nerve activity in the HFD-EXE group and increased the activity of the sympathetic nervous system in both exercised groups. Conclusion: Exercise prevents obesity and liver steatosis and restores pancreatic beta-cell function and ANS activity in HFD-obese rats.
American Journal of Physiology-Endocrinology and Metabolism, 2011
Physical activity improves glycemic control in type 2 diabetes (T2D), but its contribution to preserving β-cell function is uncertain. We evaluated the role of physical activity on β-cell secretory function and glycerolipid/fatty acid (GL/FA) cycling in male Zucker diabetic fatty (ZDF) rats. Six-week-old ZDF rats engaged in voluntary running for 6 wk (ZDF-A). Inactive Zucker lean and ZDF (ZDF-I) rats served as controls. ZDF-I rats displayed progressive hyperglycemia with β-cell failure evidenced by falling insulinemia and reduced insulin secretion to oral glucose. Isolated ZDF-I rat islets showed reduced glucose-stimulated insulin secretion expressed per islet and per islet protein. They were also characterized by loss of the glucose regulation of fatty acid oxidation and GL/FA cycling, reduced mRNA expression of key β-cell genes, and severe reduction of insulin stores. Physical activity prevented diabetes in ZDF rats through sustaining β-cell compensation to insulin resistance show...
Islets, 2016
The function and morphology of b-cells is largely dependent on insulin demand. As b-cells cover a bigger cell proportion in pancreas islets, changes of insulin producer cells affect the whole pancreatic islet morphology. Growth factors as the neurotrophins regulate the pancreas physiology, besides; physical exercise increases insulin sensitivity, and further modifies brain derived neurotrophic factor (BDNF) concentration in plasma. The aim of this study was to investigate the effects of chronic exercise (running in a treadmill for 8 weeks) intensity on pancreatic islet morphometry in healthy state. The BDNF receptor effect on the pancreatic islet morphometry was also evaluated. Adult male Wistar rats were divided in 6 groups: Control (C); moderate intensity training (MIT); high intensity training (HIT) did not treat with BDNF receptor inhibitor (K252a), and C, MIT and HIT treated with K252a. The results shown that chronic exercise induces b-cells hypertrophy without BDNF receptor participation. On the other hand, the moderate exercise increases the number of b cells per islet; the last effect does not require TrkB participation. In sedentary conditions, the K252a treatment reduced the b-cell density. Exercise intensity has differential effects on pancreas islet morphometry in healthy model; furthermore, BDNF receptor plays a role to maintain the amount of b-cells in sedentary state.
Islets
To evaluate the effect of acute exercise and exercise training at the anaerobic threshold (AT) intensity on aerobic conditioning and insulin secretion by pancreatic islets, adult male Wistar rats were submitted to the lactate minimum test (LMT) for AT determination. Half of the animals were submitted to swimming exercise training (trained), 1 h/day, 5 days/week during 8 weeks, with an overload equivalent to the AT. The other half was kept sedentary (sedentary). At the end of the experimental period, the rats were submitted to an oral glucose tolerance test and to another LMT. Then, the animals were sacrificed at rest or immediately after 20 minutes of swimming exercise at the AT intensity for pancreatic islets isolation. At the end of the experiment mean workload (% bw) at AT was higher and blood lactate concentration (mmol/L) was lower in the trained than in the control group. Rats trained at the AT intensity showed no alteration in the areas under blood glucose and insulin during ...
Diabetologia, 2018
Aims/hypothesis Pancreatic fat accumulation may contribute to the development of beta cell dysfunction. Exercise training improves whole-body insulin sensitivity, but its effects on pancreatic fat content and beta cell dysfunction are unclear. The aim of this parallel-group randomised controlled trial was to evaluate the effects of exercise training on pancreatic fat and beta cell function in healthy and prediabetic or type 2 diabetic participants and to test whether the responses were similar regardless of baseline glucose tolerance. Methods Using newspaper announcements, a total of 97 sedentary 40-55-year-old individuals were assessed for eligibility. Prediabetes (impaired fasting glucose and/or impaired glucose tolerance) and type 2 diabetes were defined by ADA criteria. Of the screened candidates, 28 healthy men and 26 prediabetic or type 2 diabetic men and women met the inclusion criteria and were randomised into 2-week-long sprint interval or moderate-intensity continuous training programmes in a 1:1 allocation ratio using random permuted blocks. The primary outcome was pancreatic fat, which was measured by magnetic resonance spectroscopy. As secondary outcomes, beta cell function was studied using variables derived from OGTT, and whole-body insulin sensitivity and pancreatic fatty acid and glucose uptake were measured using positron emission tomography. The measurements were carried out at the Turku PET Centre, Finland. The analyses were based on an intention-to-treat principle. Given the nature of the intervention, blinding was not applicable. Results At baseline, the group of prediabetic or type 2 diabetic men had a higher pancreatic fat content and impaired beta cell function compared with the healthy men, while glucose and fatty acid uptake into the pancreas was similar. Exercise training decreased pancreatic fat similarly in healthy (from 4.4% [3.0%, 6.1%] to 3.6% [2.4%, 5.2%] [mean, 95% CI]) and prediabetic or type 2 diabetic men (from 8.7% [6.0%, 11.9%] to 6.7% [4.4%, 9.6%]; p = 0.036 for time effect) without any changes in pancreatic substrate uptake (p ≥ 0.31 for time effect in both insulin-stimulated glucose and fasting state fatty acid uptake). In prediabetic or type 2 diabetic men and women, both exercise modes similarly improved variables describing beta cell function. Conclusions/interpretation Two weeks of exercise training improves beta cell function in prediabetic or type 2 diabetic individuals and decreases pancreatic fat regardless of baseline glucose tolerance. This study shows that short-term training efficiently reduces ectopic fat within the pancreas, and exercise training may therefore reduce the risk of type 2 diabetes. Marja A. Heiskanen and Kumail K. Motiani contributed equally to this study.
Physiology & Behavior, 1992
Metabolic mechanisms involved in the impaired insulin secretion in pancreatic islets isolated from exercised and fasted rats. PHYSIOL BEHAV 52(4) 723-726, 1992.-This study examined the metabolic mechanisms involved in the impaired insulin secretion by pancreatic islets isolated from fasted and exercised rats. Insulin secretion to glucose (8.3 to 16.7 mM) stimulus was lower in fasted (F), exercised (E), and fasted plus exercised (EF) rats as compared with the control group. The rate of glucose oxidation by isolated islets was reduced in F and EF rats, but it was not modified in the E group. In response to a-KIC (5, 10, 15, and 20 mM), insulin secretion was not different in EF and F rats, in comparison to controls, except in the E group, which showed values slightly higher. These findings suggest that changes in insulin secretion in fasted rats, associated or not to exercise training, might be a consequence of a reduced activity of the fight-hand side of the Krebs cycle (from pyruvate to oxoglutarate), leading to decreased glucose oxidation. However, the exercise itself caused a significant decrease of insulin secretion without altering glycolysis and Krebs cycle activities.
International Journal of Applied Pharmaceutics, 2019
Objective: This study is conducted to determine the protective effects of physical exercise and ascorbic acid on increasing blood glucose (BG) levels and islet pancreatic area in high-carbohydrate (HC) diet rats. Methods: A total of 20 rats were divided into four groups: Control group which was a HC and treatment groups which were HC plus exercise (HCEx), HC plus ascorbic acid (HCAs), and HCEx and ascorbic acid (HCExAs). The duration of treatment was 9 weeks. Swimming to exercise held 6 times a week and ascorbic acid dose was 9 mg. Results: It showed that the smallest body weight was HCEx group. BG difference (before and after treatment = BG diff) had a significant difference (p=0.021) among groups, and the lowest level of BG diff was HCEx group. HCAs had the biggest BG diff. However, there was no significantly difference among groups on islet pancreatic area, but HC group had the largest area. Conclusion: This study suggests that a combination of exercise and ascorbic acid on HC di...
Progressive histopathological changes in pancreatic islets of Zucker Diabetic Fatty rats
Experimental and Clinical Endocrinology & Diabetes, 2001
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Diabetes mellitus comprises a group of common metabolic disorders that hyperglycaemia is the common phenotype of its. Although, insulin and other glucose-lowering drugs are the most common method for treating diabetes, but also beneficial effects of exercise in regulating glucose metabolism, have been proved. Considering the effective role of exercise in diabetic patients, in this study the impact of different periods of regular moderate exercise on cardiac hypertrophy and blood glucose level were examined, to presenting a suitable pattern of exercise for diabetic patients. 60 male Wistar rats (30050g) were randomly divided into six groups (n=10): sedentary control, control with fifteen day exercise, control with sixty day exercise,sedentary diabetic , diabetic with fifteen day exercise and diabetic with sixty day exercise. Diabetes was induced by injection of streptozotocin (60 mg/Kg). The treadmill exercise 5 days a week for an hour with 22 (m/min) speeds were begun, a week after induction of diabetes. Results of this study showed that the mean blood glucose level is significantly decreased (P<0/05) by increasing the dayof exercising. And also, regular moderate exercise has prevented cardiac hypertrophy that was observed in the sedentary diabetic group. The fifteen day regular moderate exercise was not significantly reduced the blood glucose and by continuing it, blood glucose was closer to normal. Also, this type of exercise, was prevented from hypertrophy of the heart that caused by diabetes.
AJP: Endocrinology and Metabolism, 2013
Malin SK, Solomon TP, Blaszczak A, Finnegan S, Filion J, Kirwan JP. Pancreatic -cell function increases in a linear doseresponse manner following exercise training in adults with prediabetes. Although some studies suggest that a linear dose-response relationship exists between exercise and insulin sensitivity, the exercise dose required to enhance pancreatic -cell function is unknown. Thirty-five older obese adults with prediabetes underwent a progressive 12-wk supervised exercise intervention (5 days/wk for 60 min at ϳ85% HRmax). Insulin and C-peptide responses to an OGTT were used to define the first-and second-phase disposition index (DI; -cell function ϭ glucose-stimulated insulin secretion ϫ clamp-derived insulin sensitivity). Maximum oxygen consumption (V O2max) and body composition (dual-energy X-ray absorptiometry and computed tomography) were also measured before and after the intervention. Exercise dose was computed using V O2/heart-rate derived linear regression equations. Subjects expended 474.5 Ϯ 8.8 kcal/session (2,372.5 Ϯ 44.1 kcal/wk) during the intervention and lost ϳ8% body weight. Exercise increased first-and second-phase DI (P Ͻ 0.05), and these changes in DI were linearly related to exercise dose (DIfirst phase: r ϭ 0.54, P Ͻ 0.001; DIsecond phase: r ϭ 0.56, P ϭ 0.0005). Enhanced DI was also associated with increased V O2max (DIfirst phase: r ϭ 0.36, P ϭ 0.04; DIsecond phase: r ϭ 0.41, P Ͻ 0.02) but not lower body fat (DIfirst phase: r ϭ Ϫ0.21, P ϭ 0.25; DIsecond phase: r ϭ Ϫ0.30, P ϭ 0.10) after training. Low baseline DI predicted an increase in DI after the intervention (DIfirst phase: r ϭ Ϫ0.37; DIsecond phase: r ϭ Ϫ0.41, each P Ͻ 0.04). Thus, exercise training plus weight loss increased pancreatic -cell function in a linear dose-response manner in adults with prediabetes. Our data suggest that higher exercise doses (i.e., Ͼ2,000 kcal/wk) are necessary to enhance -cell function in adults with poor insulin secretion capacity. aging; obesity; insulin resistance; glucose intolerance; type 2 diabetes APPROXIMATELY 79 MILLION MEN AND WOMEN in the US are characterized as having prediabetes, of which up to 30% may develop type 2 diabetes in the next 10 years (1, 3). Although insulin sensitivity is considered a key etiological factor in the progression from prediabetes to type 2 diabetes, many insulinresistant men and women maintain normoglycemia due to compensatory rises in insulin secretion (17). Thus, preservation of pancreatic -cell function in response to glucose is fundamental to preventing type 2 diabetes, particularly in obese individuals with impaired glucose tolerance that have lost ϳ50 -70% of their -cell function . Unfortunately, the Address for reprint requests and other correspondence: J. P. Kirwan,
Early introduction of exercise prevents insulin resistance in postnatal overfed rats
Brazilian Journal of Medical and Biological Research
Early childhood obesity increases the risk of developing metabolic diseases. We examined the early introduction of exercise in small-litter obese-induced rats (SL) on glucose metabolism in the epididymal adipose tissue (AT) and soleus muscle (SM). On day 3 post-birth, pups were divided into groups of ten or three (SL). On day 22, rats were split into sedentary (S and SLS) and exercise (E and SLE) groups. The rats swam three times/week carrying a load for 30 min. In the first week, they swam without a load; in the 2nd week, they carried a load equivalent to 2% of their body weight; from the 3rd week to the final week, they carried a 5% body load. At 85 days of age, an insulin tolerance test was performed in some rats. At 90 days of age, rats were killed, and blood was harvested for plasma glucose, cholesterol, and triacylglycerol measurements. Mesenteric, epididymal, retroperitoneal, and brown adipose tissues were removed and weighed. SM and AT were incubated in the Krebs-Ringer bicarbonate buffer, 5.5 mM glucose for 1 h with or without 10 mU/mL insulin. Comparison between the groups was performed by 3-way ANOVA followed by the Tukey post-hoc test. Sedentary, overfed rats had greater body mass, more visceral fat, lower lactate production, and insulin resistance. Early introduction of exercise reduced plasma cholesterol and contained the deposition of white adipose tissue and insulin resistance. In conclusion, the early introduction of exercise prevents the effects of obesity on glucose metabolism in adulthood in this rat model.
2018
Aim: Pancreatic β-cells function and insulin sensitivity resistance were impaired in type 2 diabetes. Exercise training may improves these impairs, however, this is not well known. The aim of present study was to examine the effect of 8 weeks aerobic training on pancreatic β-cells function and insulin resistance in female patients with type 2 diabetes. Material & Methods: Twenty middle-aged women (age, 40 -50 years) with type 2 diabetes participated as the subject. The subjects were randomly assign to control group (n=10) or the training group (n=10). The subjects in the training group performed 30 to 45 min aerobic training on the treadmill with 60-75% of their maximum heart rate, 3 days a week for 8 weeks. The subjects in the control group were instructed to maintain their normal physical activity throughout the study. Results: The results indicated that fasting blood sugar, fasting insulin and insulin resistance index decrease in the training group compare to the control group (P...
Trials
Background Lifestyle intervention, i.e. diet and physical activity, forms the basis for care of type 2 diabetes (T2D). The current physical activity recommendation for T2D is aerobic training for 150 min/week of moderate to vigorous intensity, supplemented with resistance training 2–3 days/week, with no more than two consecutive days without physical activity. The rationale for the recommendations is based on studies showing a reduction in glycated haemoglobin (HbA1c). This reduction is supposed to be caused by increased insulin sensitivity in muscle and adipose tissue, whereas knowledge about effects on abnormalities in the liver and pancreas are scarce, with the majority of evidence stemming from in vitro and animal studies. The aim of this study is to investigate the role of the volume of exercise training as an adjunct to dietary therapy in order to improve the pancreatic β-cell function in T2D patients less than 7 years from diagnosis. The objective of this protocol for the DOS...
Journal of Musculoskeletal and Neuronal Interactions - JMNI, 2019
This study aimed to examine the effects of moderate (MIT) and high-intensity training (HIT) chronic exercise on plasma tumor necrosis factor alpha (TNF-α) level and its impact on Langerhans islet morphology in healthy rats. Two-month old normal male Wistar rats were divided into three groups: control (C, n=6), MIT (n=6), and HIT (n=4). The training protocol consisted in 24 sessions of running on a treadmill at 60-80% maximal oxygen consumption (VO2max) for MIT, and >80% VO2max for HIT. TNF-α and insulin were measured with ELISA tests. Duodenal pancreas was dissected to analyze the Langerhans islets by immunohistochemistry, a correlation analysis was performed with the nuclei/total islet area. Results: HIT and MIT rats showed lower TNF-α plasma levels than controls. Plasma insulin level decreased significantly in HIT compared with C and MIT. In addition, the islet area and nuclei density per islet were higher in the exercise groups compared with C. However, none of the groups show...
Objective: Apart from hormonal factors and oxidative stress, insulin synthesis is strongly dependent on transcription factors in the pancreas. The aim of the present study was to assess the impact of high-intensity interval training (HIIT) on genes affecting insulin synthesis in diabetic obese rats. Materials and Methods: Type 2 diabetes (T2D) was induced by a 6-week high-fat diet (HFD) and intraperitoneal injection of streptozotocin (25 mg /kg) in 14 male Wistar rats (10 week old, 220±10 g). Rats with fasting glucose levels between 400 and 150 were considered T2D. The diabetic rats were randomly assigned to exercise (HIIT: 6 weeks/5 sessions weekly, n= 7) or control (n= 7) groups. Forty-eight hours after the intervention, fasting GLP-1R and PKBα gene expression in pancreatic tissue and plasma insulin and glucose levels were compared between the groups. Data were compared by independent t-test used to compare variables, version 22 between groups. A P< 0.05 was considered significant. Results: HIIT led to significant increase in PKBα gene expression (P: 0.001) and insulin (P: 0.031) and decreases in glucose concentration (P: 0.001) compared with the control group. No change was observed in the GLP-1R gene expression response to HIIT (P: 0.093). Conclusion: HIIT is associated with increased serum insulin levels in T2D obese rats. Despite no change in GLP-1R, this improvement is probably rooted in increased expression PKBα in pancreas in response to this type of exercise training.
Reviewing physical exercise in non-obese diabetic Goto-Kakizaki rats
Brazilian Journal of Medical and Biological Research
There is a high incidence of non-obese type 2 diabetes mellitus (non-obese-T2DM) cases, particularly in Asian countries, for which the pathogenesis remains mainly unclear. Interestingly, Goto-Kakizaki (GK) rats spontaneously develop insulin resistance (IR) and non-obese-T2DM, making them a lean diabetes model. Physical exercise is a non-pharmacological therapeutic approach to reduce adipose tissue mass, improving peripheral IR, glycemic control, and quality of life in obese animals or humans with T2DM. In this narrative review, we selected and analyzed the published literature on the effects of physical exercise on the metabolic features associated with non-obese-T2DM. Only randomized controlled trials with regular physical exercise training, freely executed physical activity, or skeletal muscle stimulation protocols in GK rats published after 2008 were included. The results indicated that exercise reduces plasma insulin levels, increases skeletal muscle glycogen content, improves exercise tolerance, protects renal and myocardial function, and enhances blood oxygen flow in GK rats.