Exercise, unlike insulin, promotes glucose transporter translocation in obese Zucker rat muscle

Abstract

Insulin or exercise stimulates skeletal muscle glucose transport, most likely by increasing both the number and activity of glucose transporters in the plasma membrane. Skeletal muscle glucose transport of genetically obese Zucker rats (fa/fa) displays a severe insulin resistance that results, at least in part, from a failure of net transporter translocation to the cell membrane (King, P., E. D. Horton, M. Hirshman, and E. S. Horton. J. Clin, Invest. 90: 1568-1575, 1992). The purpose of the present study was to determine if the obese rat muscle was also resistant to the action of acute exercise to increase glucose transport and, if so, to determine if the defect involved transporter translocation as seen in the resistance to insulin. The muscle glucose transport system was investigated in plasma membranes isolated from postprandial, sedentary or acutely exercised, lean and obese Zucker rats. Measurements of D- and L-glucose uptake by membrane vesicles under equilibrium exchange conditions indicated that an acute bout of exercise resulted in a threefold increase in the maximum velocity (Vmax) for lean animals (5.7 vs. 17.6 nmol.mg protein-1.min-1) and a 4.5-fold increase in the Vmax for obese rats (4.1 vs. 18.6 nmol.mg protein-1.min-1). For both lean and obese animals, this increase in transport was associated with an increase in transporter number measured by cytochalasin B binding (1.6- and 2.2-fold, respectively) and with an increase in the average carrier turnover number (1.9- and 2.0-fold, respectively). The results indicate that, unlike a maximal insulin stimulus, acute exercise of the obese Zucker rat promotes both transporter translocation and transporter activation in skeletal muscle.

Exercise-Stimulated Glucose Turnover in the Rat Is Impaired by Glucosamine Infusion

“…Despite being insulinresistant, obese rats have normal increases in peripheral glucose uptake in response to moderate exercise (14,15), and similar findings have been found in obese type 2 diabetic subjects (16). These findings are not unexpected, considering it is generally accepted that exercise and insulin use different intracellular signaling pathways and recruit distinct GLUT4 transporters from different intracellular vesicular pools (13).…”

Exercise and thiazolidinedione therapy normalize insulin action in the obese Zucker fatty rat.

“…Attenuated insulin-stimulated glucose disposal resulting from decreased transport is a major manifestation of insulin resistance in ZF rats; however, the precise mechanism responsible for this defect remains unknown. This defect in glucose transport appears to be specific to insulin action because glucose uptake in response to exercise, muscle contraction, and hypoxia appear normal in these animals (6)(7)(8).…”

Effects of the nitric oxide donor, sodium nitroprusside, on resting leg glucose uptake in patients with type 2 diabetes

“…Both mechanisms increase glucose uptake via translocation of solute carrier family 2 (facilitated glucose transporter), member 4 (SLC2A4, formerly known as GLUT4), from the cytosol of the muscle cell to the plasma membrane and ttubules. Patients with type 2 diabetes [1] and insulin-resistant obese Zucker rats [2] have impaired insulin-stimulated SLC2A4 translocation; however, exercise-stimulated SLC2 A4 translocation is normal [3,4]. The signalling pathways through which these distinct mechanisms operate differ [5].…”