Exercise and adipose tissue GLUT4

Abstract

GLUT4 is the major insulin-sensitive glucose transporter expressed predominantly in skeletal & cardiac muscles, and adipose tissue (AT) and mediates insulin-stimulated glucose transport into these tissues. Due to the major role of skeletal muscle in glucose disposal, considerable attention has focused on this tissue in order to understand how glucose homeostasis is affected by changes in muscle glucose metabolism. However, AT insulin-mediated glucose uptake and GLUT4 expression have been shown to be of importance for both glucose homeostasis and whole body insulin action. Interestingly, reduced GLUT4 expression in AT is a common defect found in insulin resistant states, including obesity, metabolic syndrome, and diabetes, whereas muscle GLUT4 expression is unaltered. Exercise increases AT-GLUT4 expression in rodents, and our lab has previously shown that 4 weeks of exercise training normalizes the expression of GLUT4 in the AT of patients with T2DM. However, the mechanisms involved in exercise-induced up-regulation of AT-GLUT4 are unknown. The broad aim of my research project was to examine the effect of exercise on AT-GLUT4 expression. With this purpose, we conducted three interventions using mice, human primary adipocytes and human subjects, in an attempt to gain a better understanding of: 1) how a high fat diet (HFD) affects the expression of AT-GLUT4, 2) how exercise may be beneficial to prevent this effect; and 3) how this effect may occur. Results showed that AT-GLUT4 protein is rapidly reduced by a HFD, suggesting this could be an early defect contributing to HFD-induced insulin resistance; exercise training increases GLUT4 protein in HFD-fed mice, short-term (10 d) exercise training did not affect GLUT4 levels in human, subcutaneous AT; and serum from exercised subjects increased GLUT4 protein and mRNA in human primary adipocytes suggesting that circulating factor(s) may mediate exercise effects on AT GLUT4 expression.

Adipose tissue (AT) glucose transporter GLUT4 is reduced in insulin resistance (IR). Exercise training (EX) (4 weeks) normalized AT-GLUT4 expression in diabetic patients. However, mechanisms involved are unknown. Results showed: 1) AT-GLUT4 is reduced by high fat diet (HFD), which may contributes IR; 2) EX increased GLUT in HFD-fed mice, 3) short-term (10 d) EX didn’t affect GLUT4 in human AT; and 4) exercise serum increased GLUT4 in human primary adipocytes, suggesting circulating factor(s) may mediate EX-effects on AT GLUT4.