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Genetic reduction of skeletal muscle glycogen synthase 1 abundance reveals that the refeeding-induced reversal of elevated insulin-stimulated glucose uptake after exercise is not attributable to achieving a high muscle glycogen concentration.
FASEB J
November 2024
Muscle Biology Laboratory, School of Kinesiology, University of Michigan, Ann Arbor, Michigan, USA.
One exercise session can increase subsequent insulin-stimulated glucose uptake (ISGU) by skeletal muscle. Postexercise refeeding induces reversal of postexercise (PEX)-enhanced ISGU concomitant with attaining high muscle glycogen in rats. To test the relationship between high glycogen and reversal of PEX-ISGU, we injected one epitrochlearis muscle from each rat with adeno-associated virus (AAV) small hairpin RNA (shRNA) that targets glycogen synthase 1 (GS1) and injected contralateral muscles with AAV-shRNA-Scrambled (Scr).
View Article and Find Full Text PDFPhosphorylation of AS160-serine 704 is not essential for exercise-increase in insulin-stimulated glucose uptake by skeletal muscles from female or male rats.
Am J Physiol Endocrinol Metab
June 2024
Muscle Biology Laboratory, School of Kinesiology, University of Michigan, Ann Arbor, Michigan, United States.
One exercise session can increase subsequent insulin-stimulated glucose uptake (ISGU) by skeletal muscle from rodents and humans of both sexes. We recently found that concurrent mutation of three key sites to prevent their phosphorylation (Ser588, Thr642, and Ser704) on Akt substrate of 160 kDa (AS160; also known as TBC1D4) reduced the magnitude of the enhancement of postexercise ISGU (PEX-ISGU) by muscle from male, but not female rats. However, we did not test the role of individual phosphorylation sites on PEX-ISGU.
View Article and Find Full Text PDFSucrose-Enriched and Carbohydrate-Free High-Fat Diets Distinctly Affect Substrate Metabolism in Oxidative and Glycolytic Muscles of Rats.
Nutrients
January 2024
Muscle Health Research Centre, School of Kinesiology and Health Science, York University, Toronto, ON M3J 1P3, Canada.
Skeletal muscle substrate preference for fuel is largely influenced by dietary macronutrient availability. The abundance of dietary carbohydrates promotes the utilization of glucose as a substrate for energy production, whereas an abundant dietary fat supply elevates rates of fatty acid (FA) oxidation. The objective of this study was to determine whether an obesogenic, high-fat, sucrose-enriched (HFS) diet or a carbohydrate-free ketogenic diet (KD) exert distinct effects on fat, glucose, and ketone metabolism in oxidative and glycolytic skeletal muscles.
View Article and Find Full Text PDFInsulin-resistant female rat skeletal muscles display diacylglycerol-mediated protein kinase C activation and inflammation without ceramide accumulation.
J Physiol
May 2023
Muscle Health Research Center - School of Kinesiology and Health Science, York University, North York, Ontario, Canada.
This study investigated the role of diacylglycerol (DAG)-mediated protein kinase C (PKC) activation, ceramide accumulation and inflammation in insulin-resistant female oxidative and glycolytic skeletal muscles induced by an obesogenic high-fat sucrose-enriched (HFS) diet. The HFS diet impaired insulin-stimulated AKT phosphorylation and glycogen synthesis, whereas rates of fatty acid oxidation and basal lactate production were significantly elevated in soleus (Sol), extensor digitorum longus (EDL) and epitrochlearis (Epit) muscles. Insulin resistance was accompanied by increases in triacylglycerol (TAG) and DAG contents in Sol and EDL, whereas in Epit muscles only TAG content and markers of inflammation were associated with HFS diet-induced insulin resistance.
View Article and Find Full Text PDFAkt substrate of 160 kDa is essential for the calorie restriction-induced increase in insulin-stimulated glucose uptake by skeletal muscle of female rats.
Appl Physiol Nutr Metab
March 2023
Muscle Biology Laboratory, School of Kinesiology, University of Michigan, Ann Arbor, MI, USA.
We evaluated effects of calorie restriction (CR; consuming 65% of ad libitum (AL) intake) for 8 weeks on female wildtype (WT) and Akt substrate of 160 kDa knockout (AS160-KO) rats. Insulin-stimulated glucose uptake (ISGU) was determined in isolated epitrochlearis muscles incubated with 0, 50, 100, or 500 µU/mL insulin. Phosphorylation of key insulin signaling proteins that control ISGU (Akt and AS160) was assessed by immunoblotting (Akt phosphorylation on Threonine-308, pAkt and Serine-473, pAkt; AS160 phosphorylation on Serine-588, pAS160, and Threonine-642, pAS160).
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