Exercise increases hexokinase II mRNA, but not activity in obesity and type 2 diabetes

Glucose phosphorylation, catalyzed by hexokinase, is the first committed st ep in glucose uptake in skeletal muscle. Hexokinase II (HKII) is the isofor m that is present in muscle and is regulated by insulin and muscle contract ion. Glucose phosphorylation and HKII expression are both reduced in obese and type 2 diabetic subjects. A single bout of exercise increases HKII mRNA and activity in muscle from healthy subjects. The present study was perfor med to determine if a moderate exercise increases HKII mRNA expression and activity in patients with type 2 diabetes. Muscle biopsies were performed b efore and 3 hours after a single bout of cycle ergometer exercise in obese and type 2 diabetic patients. HKII mRNA and activity and glycogen synthase activity were determined in the muscle biopsies. Exercise increased HKII mR NA in obese and diabetic subjects by 1.67 +/- 0.34 and 1.87 +/- 0.26-fold, respectively (P < .05 for both). Exercise did not significantly increase HK I mRNA, When HKII mRNA increases were compared with the 2.26 +/- 0.36-fold increase in HKII mRNA previously reported for healthy lean subjects, no sta tistically significant differences were found, In contrast to the increase in HKII activity observed after exercise by lean healthy controls, exercise did not increase HKII activity in obese nondiabetic or diabetic subjects. Exercise increased glycogen synthase activity (GS(0.1) and GS(FV)) signific antly in both obese nondiabetic and type 2 diabetic patients. The present r esults indicate that there is a posttranscriptional defect in the response of HKII expression to exercise in obese and type 2 diabetic subjects. This defect may contribute to reduced HKII activity and glucose uptake in these patients. Copyright (C) 2001 by W.B. Saunders Company.