Effects of overexpressed, constitutively-active glycogen synthase on whole body glucose tolerance and insulin-stimulated glucose metabolism
Year: 2002
Type: dissertation
Abstract: Using the GSL3 transgenic mouse model, we have provided evidence that muscle glycogen concentration, per se, does not affect post-exercise insulin action in vivo or in muscle using an in situ preparation.Transgenic gastrocnemius muscle had significantly greater (7-fold) muscle glycogen concentration compared to wildtype.Glycogen concentration was unchanged 24 h following exhaustive exercise.In vivo insulin action during an intraperitoneal glucose tolerance test was improved 24 h following exercise regardless of the muscle glycogen concentration.Resting insulin-stimulated muscle glucose uptake was 30% lower in non-exercised transgenic versus wildtype muscle.Insulinstimulated muscle glucose uptake was improved 24 h following exercise in Abstract Using a unique mouse model that overexpresses glycogen synthase, we have re-investigated the effects of muscle glycogen concentration on glucose tolerance and insulin-stimulated glucose uptake pre-and post-exercise.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.TG gastrocnemius muscle had 7-fold greater muscle glycogen concentration compared to WT. Glycogen concentration was unchanged from pre-exercise values 24 h following the exercise/dietary manipulation in WT and TG.In vivo insulin action was improved following exercise regardless of the muscle glycogen concentration.Resting insulin-stimulated muscle glucose uptake was 30% lower in non-exercised TG versus WT muscle.Post-exercise insulin-stimulated glucose uptake was improved in TG (84%) but not WT.PI3-kinase and PKB/Akt activation was similar in nonand post-exercise WT and TG muscle.However, insulin-stimulated glucose uptake and activation of PKB/Akt were reduced in SUPER muscle.Using the GSL3 transgenic mouse model, we have provided evidence that muscle glycogen concentration, per se, does not affect post-exercise insulin action in vivo or in muscle using an in situ preparation.
Author: Donovan L. Fogt
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2105287550