Voluntary running exercise prevents β-cell failure in susceptible islets of the Zucker diabetic fatty rat

Abstract

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 shown in vivo and in vitro. Surprisingly, ZDF-A islets had persistent defects in fatty acid oxidation, GL/FA cycling, and β-cell gene expression. ZDF-A islets, however, had preserved islet insulin mRNA and insulin stores compared with ZDF-I rats. Physical activity did not prevent hyperphagia, dyslipidemia, or obesity in ZDF rats. In conclusion, islets of ZDF rats have a susceptibility to failure that is possibly due to altered β-cell fatty acid metabolism. Depletion of pancreatic islet insulin stores is a major contributor to islet failure in this T2D model, preventable by physical activity.

Self-Reported Physical Activity Is Associated With β-Cell Function in Mexican American Adults

“…Therefore, our results indicated a more direct contribution of PA in preserving β-cell function. Moreover, our findings are consistent with the results of a recent study in rats, which demonstrated that voluntary exercise was beneficial for sustaining β-cell compensation without preventing dyslipidemia or obesity (35). One possible mechanism for such an effect would be mitigation of the adverse metabolic effects of obesity.…”

Intermittent walking, but not standing, improves postprandial insulin and glucose relative to sustained sitting: A randomised cross-over study in inactive middle-aged men

“…Improvement in Matsuda index and reduced insulin levels with intermittent walking is consistent with previous observations of the preservation of beta-cell function by conservation of pancreatic insulin stores with physical activity. 25 Importantly, the lowering of glucose and insulin with intermittent walking was most distinguishable in the postprandial periods. Postprandial hyperglycaemia may be a better predictor of CVD mortality than fasting hyperglycaemia 26 and blunting of postprandial glucose is shown to reduce intima media thickness, oxidative stress, inflammation and endothelial dysfunction.…”

Beta Cell Dysfunction and Insulin Resistance

“…Exercise maintained or enhanced beta cell function in older obese individuals, with improved beta cell function correlating with reduced glucose concentrations (Malin and Kirwan, 2012). In the ZDF rat, voluntary running prevented the development of diabetes despite continuing hyperphagia, obesity, and hyperlipidemia (Delghingaro-Augusto et al, 2012). Compensatory insulin secretion was preserved and hyperglycemia prevented by exercise was characterized by enhanced insulin secretion per islet and the prevention of severe depletion of islet insulin stores (Delghingaro-Augusto et al, 2012).…”

“…In the ZDF rat, voluntary running prevented the development of diabetes despite continuing hyperphagia, obesity, and hyperlipidemia (Delghingaro-Augusto et al, 2012). Compensatory insulin secretion was preserved and hyperglycemia prevented by exercise was characterized by enhanced insulin secretion per islet and the prevention of severe depletion of islet insulin stores (Delghingaro-Augusto et al, 2012). Frequent exercise and adopting a healthy diet is a strategy to improve diabetic outcomes, particularly in pre-diabetic states such as obesity and/or insulin resistance and beta cell dysfunction.…”