To Reveal the Mechanism of Exercise-Induced Delayed Onset of Hypoglycemia in Type 1 Diabetes　− For Development of New Exercise Guideline in Type 1 Diabetes Patients −

Abstract

Type 1 diabetes patients often suffered from exercise-induced hypoglycemia especially, nocturnal and delayed onset of hypoglycemia after exercise. In the present study, we characterized potential mechanisms for the development of delayed onset of exercise-induced hypoglycemia in type 1 diabetes by performing animal studies. We assessed the blood glucose levels and glucose metabolic pathway activation over time in streptozotocin （STZ） injected rats, STZ rats with exercise （STZ+EX），and control rats with exercise （CON+EX）．Moreover, samples were taken at 1h, 3h and 5h after exercise in three groups, and was used for microarray analysis. Although blood glucose levels of STZ rats and CON+EX rats did not differ significantly before and after exercise （0 h to 5 h）， the blood glucose levels of STZ+EX rats were significantly lower than those of STZ group at 3 h （P < 0.05）．In skeletal muscles, Akt phosphorylation level and GLUT4 translocation were significantly increased at 1 h in both CON and STZ groups and were lowered to negligible levels within 3 h. In contrast, in the STZ+EX group, Akt phosphorylation, and GLUT4 translocation was maintained by 5 h, indicating sustained glucose metabolism in STZ+EX group. In microarray analysis, 447 genes of insulin signaling and 79 genes of type 1 diabetes were found in this study, and selected 3 genes which may concern GLUT4 regulation, especially Oncostatin M（Osm） and signal transducer and activator of transcription 3（STAT3） were increased at 3h and 5h after exercise in STZ+EX group. In summary, we showed that a single bout of aerobic exercise induced prolonged enhancement of GLUT4 translocation may be involved in the induction of hypoglycemia.