Insulin Resistance Does Not Impair Mechanical Overload-Stimulated Glucose Uptake, but Does Alter the Metabolic Fate of Glucose in Mouse Muscle

International Journal of Molecular Sciences

LukeA. Weyrauch¹  ShawnaL. McMillin¹  CarolA. Witczak¹ 

[1] Department of Kinesiology, East Carolina University, Greenville, NC 27858, USA;

关键词: exercise;    glucose transporter;    glycogen;    glycolysis;    hexosamine pathway;    lactate;   

DOI  :  10.3390/ijms21134715

来源: DOAJ

【 摘 要 】

Skeletal muscle glucose uptake and glucose metabolism are impaired in insulin resistance. Mechanical overload stimulates glucose uptake into insulin-resistant muscle; yet the mechanisms underlying this beneficial effect remain poorly understood. This study examined whether a differential partitioning of glucose metabolism is part of the mechanosensitive mechanism underlying overload-stimulated glucose uptake in insulin-resistant muscle. Mice were fed a high-fat diet to induce insulin resistance. Plantaris muscle overload was induced by unilateral synergist ablation. After 5 days, muscles were excised for the following measurements: (1) [³H]-2-deoxyglucose uptake; (2) glycogen; 3) [5-³H]-glucose flux through glycolysis; (4) lactate secretion; (5) metabolites; and (6) immunoblots. Overload increased glucose uptake ~80% in both insulin-sensitive and insulin-resistant muscles. Overload increased glycogen content ~20% and this was enhanced to ~40% in the insulin-resistant muscle. Overload did not alter glycolytic flux, but did increase muscle lactate secretion 40–50%. In both insulin-sensitive and insulin-resistant muscles, overload increased 6-phosphogluconate levels ~150% and decreased NADP:NADPH ~60%, indicating pentose phosphate pathway activation. Overload increased protein O-GlcNAcylation ~45% and this was enhanced to ~55% in the insulin-resistant muscle, indicating hexosamine pathway activation. In conclusion, insulin resistance does not impair mechanical overload-stimulated glucose uptake but does alter the metabolic fate of glucose in muscle.

【 授权许可】

Unknown