Showing papers by "Michael F. Hirshman published in 1995"

Mechanisms and time course of impaired skeletal muscle glucose transport activity in streptozocin diabetic rats.

Abstract: Skeletal muscle glucose transport is altered in diabetes in humans, as well as in rats. To investigate the mechanisms of this abnormality, we measured glucose transport Vmax, the total transporter number, their average intrinsic activity, GLUT4 and GLUT1 contents in skeletal muscle plasma membrane vesicles from basal or insulin-stimulated streptozocin diabetic rats with different duration of diabetes, treated or not with phlorizin. The glucose transport Vmax progressively decreased with the duration of diabetes. In the basal state, this decrease was primarily associated with the reduction of transporter intrinsic activity, which appeared earlier than any change in transporter number or GLUT4 and GLUT1 content. In the insulin-stimulated state, the decrease of transport was mainly associated with severe defects in transporter translocation. Phlorizin treatment partially increased the insulin-stimulated glucose transport by improving the transporter translocation defects. In conclusion, in streptozocin diabetes (a) reduction of intrinsic activity plays a major and early role in the impairment of basal glucose transport; (b) a defect in transporter translocation is the mechanism responsible for the decrease in insulin-stimulated glucose transport; and (c) hyperglycemia per se affects the insulin-stimulated glucose transport by altering the transporter translocation.

Mechanisms of Increased Skeletal Muscle Glucose Transport Activity After an Oral Glucose Load in Rats

Abstract: It is not known whether the insulin-induced changes in the skeletal muscle glucose transport system occur under physiological circumstances. To clarify whether, by which mechanisms, and for howlong skeletal muscle glucose transport activity is increased after an oral glucose load (OGL), we prepared plasma membrane (PM) and microsomal membrane (MsM) vesicles from hindlimb muscles of Sprague-Dawley rats either in the fasting state or 30, 60, 90, or 120 min after an OGL (2 g/kg body wt). In both PM and MsM, we measured the total number of glucose transporters ( R o ), GLUT4, and GLUT1. In the PM, we also determined glucose influx (V max ) and carrier turnover number (TN), an index of average transporter intrinsic activity, (TN = V max / R o ). The V max significantly increased after OGL, was maximal at 30 min, and returned to baseline at 90 min. The R o and GLUT4 in the PM also increased significantly, with themaximum level reached at 60 min. The TN was increased only at 30 min. The changes in R o andGLUT4 in the MsM were opposite to those in the PM, consistent with translocation of GLUT4 from an intracellular pool to the PM. In conclusion, an OGL induces an increase in the skeletal muscle glucose transport activity. This increase is associated with the translocation of GLUT4 from the MsM to the PM and a more transient increase in the average transporter TN. Our results show that transporter translocation and activation occur under physiological circumstances.