Regulation of Glucose Uptake in Muscle

Abstract

It was concluded in earlier papers (l-7) that the transport of glucose through the cell membrane and the phosphorylation of free glucose inside the cell are the major rate-controlling steps for glucose uptake by the heart. In the muscle from severely diabetic animals, glucose uptake was very low. This could be attributed to a low rate of transport, which is principally limiting for uptake under these conditions. When insulin was added, transport was strongly stimulated but glucose uptake increased only moderately and the rate remained much below that reached in a normal heart similarly treat,ed. The poor response to insulin could be explained by a marked depression of phosphorylation, which imposes the major limitation on the rate of uptake after transport acceleration. The phosphorylation step seemed to be insensitive to insulin in vitro. The low transport activity in the heart muscle of the diabetic rat was found by Morgan et al. (8) to be caused by a deficiency of insulin and not by a direct inhibition by pituitary and adrenal cortical factors. A similar conclusion was reached by Kipnis (9) and Kipnis and Cori (lo), who measured the penetration of 2-deoxyglucose in the rat diaphragm. Morgan et al. (5), Park and Morgan (7), and Henderson et al. (11, 12) concluded, however, that pituitary and adrenal factors may affect transport indirectly by interfering with the action of insulin. The depression of phosphorylation in the diabetic muscle was attributed to pituitary and adrenal cortical activity (8-10). Morgan et al. (8) showed that growth hormone and hydrocortisone were among the hormones involved. The present paper gives a further exposition of how pituitary and adrenal cortical secretions, including the growth hormone and hydrocortisone, influence glucose uptake in the perfused heart. The effect of these factors and of insulin on the transport and phosphorylation steps individually is considered. From these observations, some general concepts are advanced concerning the regulation of peripheral glucose utilization in the intact animal under a variety of conditions.