Endurance Training Activates Pancreatic Islets Amp-Activated Kinase-Uncoupling Protein 2 Pathway and Reduces Insulin Secretion

Abstract

Endurance exercise is known to enhance peripheral insulin sensitivity and reduce insulin secretion. However, it is unknown whether the latter effect is due to the reduction in plasma substrate availability or alterations in b-cell secretory machinery. Here, we tested the hypothesis that endurance exercise reduces insulin secretion by altering the intracellular energy-sensitive AMP-activated kinase (AMPK) signaling pathway. Male Wistar rats were submitted to endurance protocol training one, three, or five times per week, over 8 weeks. After that, pancreatic islets were isolated, and glucose-induced insulin secretion (GIIS), glucose transporter 2 (GLUT2) protein content, total and phosphorylated calmodulin kinase kinase (CaMKII), and AMPK levels as well as peroxisome proliferator-activated receptor-g coactivator-1-a (PGC-1a) and uncoupling protein 2 (UCP2) content were measured. After 8 weeks, chronic endurance exercise reduced GIIS in a dose-response manner proportionally to weekly exercise frequency. Contrariwise, increases in GLUT2 protein content, CaMKII and AMPK phosphorylation levels were observed. These alterations were accompanied by an increase in UCP2 content, probably mediated by an enhancement in PGC-1a protein expression. In conclusion, chronic endurance exercise induces adaptations in b-cells leading to a reduction in GIIS, probably by activating the AMPK signaling pathway.

Glycolytic and Mitochondrial Metabolism in Pancreatic Islets from MSG-Treated Obese Rats Subjected to Swimming Training

“…Similar results were obtained for pancreatic islets isolated from diabetic Goto-Kakizaki (GK)-exercised rats (treadmill, 5 days/week, for 9 weeks) [43]. However, increase in GLUT2 expression in pancreatic islets was observed in lean trained rat (treadmill; 1, 3 or 5 times per week; for 8 weeks) [44]. In pancreatic islets from the CON-EXE (lean) group, we also observed an increase in GLUT2 expression, but this effect was not significant.…”

“…However, in our results, islets obtained from exercise rats shows reduced glucose-induce insulin secretion. Recently, increased levels of uncoupling protein 2 (UCP2) were observed in isolated pancreatic islets from exercised rats, which could be involved in reduced glucose-induced insulin secretion [44]. In addition, studies have shown that over-expression of UCP2 in an insulin-producing cell line increase mitochondrial respiration while decreasing the coupling to oxidative phosphorylation; this effect results in a low intracellular ATP level and reduced glucose-induced insulin secretion [59].…”

Moderate Exercise Restores Pancreatic Beta-Cell Function and Autonomic Nervous System Activity in Obese Rats Induced by High-Fat Diet

“…In addition, our results showed that moderate exercise increased insulin sensitivity and reduced insulin secretion in the HFD-treated group. This was determined by the response of isolated pancreatic islets to basal and stimulatory glucose concentrations and is similar to other studies where swimming or endurance training was used [7,18]. …”

“…Thereafter, the constant rate for glucose disappearance (K itt ) was calculated by the formula 0.693/(t 1/2 ). The plasma glucose t 1/2 was calculated from the slope of the least-squares analysis of plasma glucose concentrations during the linear decay phase [18]. Anesthesia was not used during the ivGTT or ipITT tests.…”

“…The Krebs solution was then replaced, and islets were incubated for 60 min under the experimental conditions with 5.6 mM, 8.3 mM, 11.1 mM and 16.7 mM glucose to assess GIIS. The insulin secretion was determined by RIA [18]. …”