The impact of sulfonylurea treatment upon the mechanisms responsible for the insulin resistance in type II diabetes.

Insulin resistance is a characteristic feature of patients with type II diabetes mellitus as well as patients with impaired glucose tolerance (IGT). The cause of the insulin resistance in patients with IGT appears to be solely related to a decrease in the number of cellular insulin receptors, causing a decrease in insulin sensitivity. On the other hand, the mechanisms of the insulin resistance in patients with type II diabetes mellitus are heterogeneous; in these subjects a combination of receptor and postreceptor defects exists, and the relative contribution of these two abnormalities to the overall insulin-resistant state differs depending on the severity of the diabetes. In those patients with the greatest degree of fasting hyperglycemia, the postreceptor defect is clearly the predominant abnormality. In addition to resistance to insulin's effects to promote glucose disposal, type II diabetic patients also exhibit a marked increase in the rate of entry of glucose into the circulation from the liver, as manifested by accelerated rates of hepatic glucose production. Sulfonylureas exert potent extrapancreatic effects that partially correct all of the abnormalities present in the type II diabetic state. Thus, after 3 mo of glyburide treatment, glycemic control is markedly improved and this is accompanied by an increase in insulin secretion, no change in cellular insulin receptors, decreased hepatic glucose production rates, and an increase in overall insulin-mediated glucose disposal. After 18 mo of glyburide treatment, an increase in insulin secretion can no longer be demonstrated, whereas insulin binding to receptors is now significantly increased.(ABSTRACT TRUNCATED AT 250 WORDS)