Effects of chronic exercise on muscle and liver glucose metabolism and sestrin proteins in diabetic aged female rat model

The aim of this study is to investigate the effects of chronic exercise on muscle and liver glucose metabolism and sestrin proteins in a diabetic elderly female rat model. In this study, GLUT-4, SESN-1, SESN-2 and SIRT-1 gene expression levels were examined in muscle and liver tissues in order to determine the effects of chronic exercise on glucose metabolism in old age. The research protocol was initiated after approval by the Selcuk University Experimental Medicine Research and Application Center (SUDAM) Experimental Animals Ethics Committee (2022/22). The study was conducted on 40 Wistar aged female rats obtained from SUDAM. The experimental animals used in the study were randomly divided into 4 groups: Group 1: Control Group (n=10); Group 2: Exercise Control Group (n=10); Group 3: Diabetic Control Group (n=10); Group 4: Diabetes + Exercise Group (n=10). In the study, diabetes was induced by subcutaneous administration of 40 mg/kg streptozotocin (STZ) to rats (G3 and G4) that were separated to create diabetes. After confirming the formation of diabetes in rats, exercise groups (G2 and G4) were made to run on a rat treadmill for 45 minutes daily at 20 m/s speed for 4 weeks. 24 hours after the last running exercise, the experimental animals constituting our study groups were sacrificed under general anesthesia and muscle and liver tissue samples were taken. Real-Time Polymerase Chain Reaction (qPCR) protocols were applied to detect mRNA expression of SESN-1, SESN-2, SIRT-1 and GLUT-4 genes in the tissue samples taken. Analysis results were evaluated using the delta-delta Ct (2-ΔΔCt) method and the results were recorded as fold change. SPSS 26.0 package program was used for statistical evaluation of the study results. Differences at the level of P<0.05 were considered significant. In the study, the highest SESN-1 and SESN-2 levels in muscle tissue were determined in the diabetic control group (G3), while the lowest value was recorded in the exercise control group (G2). It was observed that muscle tissue SESN-1/2 levels of exercise groups (G2 and G4) were significantly lower compared to controls (G1 and G3). Diabetes and old age significantly increased SESN-1 and SESN-2 levels in muscle tissue, while exercise decreased them (P<0.05). In our study, the highest SIRT-1 and GLUT-4 expression levels in muscle tissue were detected in G2, while the lowest levels were recorded in G3. It was determined that exercise groups (G2 and G4) exhibited significantly higher muscle tissue SIRT-1 and GLUT-4 expression compared to control groups (G1 and G3). Diabetes significantly decreased SIRT1 and GLUT4 levels in muscle tissue, while exercise increased them (P<0.05). In the study, the highest SESN-1 and SESN-2 gene expression in liver tissue was detected in the diabetic control group (G3). SESN-1 and SESN-2 levels in the diabetes + exercise group (G4) were significantly higher than the control (G1) and exercise control (G2) groups, and significantly lower than the diabetic control group (G3). Diabetes and old age significantly increased SESN-1 and SESN-2 levels in liver tissue, while exercise decreased them (P<0.05). In our study, the highest SIRT-1 and GLUT-4 gene expression levels in liver tissue were detected in G2, while the lowest value was detected in G3. It was determined that the exercise groups (G2 and G4) exhibited significantly higher liver SIRT-1 and GLUT-4 gene expression compared to the control groups (G1 and G3). Diabetes significantly decreased SIRT-1 and GLUT-4 levels in liver tissue, while exercise increased them (P<0.05). Chronic exercise in aged female rats regulates metabolic stress caused by diabetes and aging in both muscle and liver and significantly reduces mRNA levels of stress-adaptive proteins (SESN-1 and SESN-2). On the other hand, SIRT-1, which increases with exercise in the muscle and liver of exercising rats, provides a molecular explanation for the improved metabolic profile. Our findings show that exercise increases GLUT-4 levels in muscle and liver, facilitating glucose transport and alleviating the adverse metabolic effects of diabetes. In conclusion, the adverse metabolic profile of diabetes and aging is either reversed or partially improved in muscle and liver tissue through chronic exercise. Our study showed that chronic exercise in the management of advanced age diabetes benefits glucose metabolism through different metabolic health markers at multiple tissue levels.