Insulin augmentation of glucosestimulated insulin secretion is impaired in insulin-resistant humans

Type 2 diabetes (T2D) is characterized by insulin resistance and pancreatic b-cell dysfunction, the latter possibly caused by a de-fect in insulin signaling in b-cells. We hypothesized that insulin’s effect to potentiate glucose-stimulated insulin secretion (GSIS) would be diminished in insulin-resistant persons. To evaluate the effect of insulin to modulate GSIS in insulin-resistant com-pared with insulin-sensitive subjects, 10 participants with im-paired glucose tolerance (IGT), 11 with T2D, and 8 healthy control subjects were studied on two occasions. The insulin se-cretory response was assessed by the administration of dextrose for 80 min following a 4-h clamp with either saline infusion (sham) or an isoglycemic-hyperinsulinemic clamp using B28-Asp-insulin (which can be distinguished immunologically from endogenous insulin) that raised insulin concentrations to high physiologic concentrations. Pre-exposure to insulin augmente