Effects of Streptozotocin-induced Diabetes on Insulin Binding, Glucose Transport, and Intracellular Glucose Metabolism in Isolated Rat Adipocytes

Abstract

Insulin receptors and various aspects of glucose metabolism were studied in isolated adipocytes from insulin-deficient streptozotocin (STZ)-treated diabetic rats. Severe diabetes was induced by high dose (55 mg/kg) STZ administration and mild diabetes was induced by low dose (40 mg/kg) STZ treatment. The high dose STZ group (morning plasma glucose level of 511 ± 32 mg/dl) became markedly catabolic and gained weight at a rate of only 0.6 ± 0.9 g/day as compared with 6.7 ± 0.8 g/day for controls. The low dose STZ group gained weight at a near normal rate (5.8 ± 0.7 g/day) despite modest hyperglycemia (morning plasma glucose 214 ± 36 ng/100 ml) and hypoinsulinemia. Insulin binding to receptors was increased 25% in the low dose group due to greater receptor capacity with no change in affinity and was increased 105% in the high dose group due to enhanced receptor affinity and capacity. Glucose transport activity was decreased in adipocytes from the diabetic animals, and, in addition, all aspects of intracellular glucose metabolism studied were depressed. These effects were greatest in the high dose group. In summary, (a) in severely diabetic, catabolic animals, insulin binding to receptors is increased due to enhanced receptor capacity and affinity; in mildly diabetic rats only receptor capacity is increased; (b) glucose transport activity and intracellular pathways of glucose metabolism are impaired in insulin-deficient diabetic animals, most likely due to hypoinsulinemia; and (c) the cellular insulin resistance of insulin-deficient diabetes is due to multiple defects in effector systems distal to the insulin receptor.