Effects of Glycogen Synthase Overexpression on Post-Exercise Glucose Tolerance and Insulin-Stimulated Muscle Glucose Uptake

Abstract

2264 GSL3 transgenic mice overexpress a constitutively active form of glycogen synthase which is associated with an abundant storage of muscle glycogen. Using this unique mouse model, we have investigated the effects of muscle glycogen concentration on glucose tolerance and insulin-stimulated muscle glucose uptake pre- and postexercise. PURPOSE: To determine the effects of muscle glycogen concentration on glucose tolerance and insulin-stimulated glucose uptake. METHODS: GSL3 transgenic (TG) mice, wildtype (WT) and glycogen supercompensated wildtype (SUPER) mice were studied using an intraperitoneal glucose tolerance test and hindlimb perfusion technique at rest or following two successive days of exhaustive exercise with carbohydrate restriction. RESULTS: Gastrocnemius muscle glycogen was 7-fold greater in TG and 3-fold greater in SUPER compared with WT. Glycogen concentration was unchanged from pre-exercise values 24 h following the exercise/dietary manipulation in WT and TG. Glucose tolerance and in vivo insulin action were not affected by muscle glycogen. Prior exercise had no effect on glucose tolerance, but improved in vivo insulin action. Pre-exercise insulin-stimulated muscle glucose uptake was 30% lower in non-exercised TG versus WT muscle. However, postexercise insulin-stimulated glucose uptake was similar for TG and WT. PKB/Akt activity was similar in pre- and post-exercised WT and TG muscle, with PKB/Akt activity increasing post-exercise in the presence of a submaximal insulin concentration (0.2 mU/ml). However, insulin-stimulated glucose uptake and activation of PKB/Akt were both reduced in SUPER muscle. CONCLUSION: The results indicate that muscle glycogen concentration, per se, does not affect post-exercise insulin action in vivo or insulin-stimulated muscle glucose uptake, but that activation of PKB/Akt may be essential for insulin-stimulated muscle glucose uptake. Supported by ACSM Foundation Research Grant FRG13