Heat-Shock Protein 70-Mediated Heat Preconditioning Attenuates Hepatic Carbohydrate and Oxidative Disturbances in Rats With Type 1 Diabetes.

Objectives: Heat preconditioning and heat-shock protein (HSP) synthesis have significant cytoprotective effects against the development of cellular injury caused by the application of a subsequent stressor, which were found to depend on the time period between the stressors. We aimed to determine the most efficient recovery time (6 h or 24 h) following heat-stress exposure and prior application of diabetic streptozotocin (STZ) on the moderation of carbohydrate and oxidative metabolic disturbances caused by diabetes.

Methods: Experiment animals (Wistar rats) were exposed to acute heat stress at 41±1°C for 45 min, followed by 6-h or 24-h recovery times at room temperature before sacrifice or STZ administration.

Results: Our findings indicate that acute heat stress with 6-h or 24-h recovery periods results in a significant rise in the hepatic heat-shock protein 70 (HSP70) levels (even more so after 24 h), glycogen breakdown and stable glycemia, followed by reduced glycolytic and gluconeogenic activity (after 24 h) (glucose-6-phosphatase, fructose-1,6-bisphosphatase); stimulates antioxidative activity (glutathione peroxidase, glutathione reductase) (after 6 h); and decreases glutathione and catalase activity (after 24 h). Heat preconditioning (with 6-h and 24-h recovery periods) prior to STZ-induced diabetes increases HSP70 levels and causes lower serum glucose levels, higher glycogen and glucose-6-phosphate levels, lower glucose-6-phosphatase levels and glycogen phosphorylase and hexokinase levels but also elevates glutathione reductase and glutathione peroxidase activity compared to untreated STZ animals.

Conclusions: Based on our findings, heat preconditioning and HSP70 induction in rats with type 1 diabetes attenuates STZ-induced metabolic alterations in hepatic carbohydrate metabolism and oxidative states. These changes are more evident at 24 h recovery post-acute heat stress, based on the most evident accumulation of HSP70 in this time frame.