Insulin receptor function and insulin effects on glucose metabolism in adipocytes from ventromedial...

To investigate the mechanism of the development of insulin resistance in hypothalamic obesity, we studied insulin binding, glucose transport, and glucose oxidation in adipocytes from ventromedial hypothalamus (VMH)-lesioned rats 1 and 2 weeks after injury. One week after injury, insulin binding and insulin-stimulated glucose oxidation were increased, but insulin-stimulated glucose transport was similar to control. Two weeks after injury, insulin binding and insulin-stimulated glucose transport were similar to control, but insulin-stimulated glucose oxidation was decreased. Thus, cellular insulin responsiveness was increased in adipocytes from VMH-lesioned rats 1 week after injury; this increase in insulin responsiveness was due mainly to the increased intracellular glucose metabolism. On the other hand, cellular insulin resistance existed in adipocytes from VMH-lesioned rats 2 weeks after injury; this insulin resistance was also due mainly to a defect in intracellular glucose metabolism.