Halperin, FlorenciaLopez, XimenaManning, RaquelKahn, C.Kulkarni, RohitGoldfine, Allison B.2013-10-292012Halperin, Florencia, Ximena Lopez, Raquel Manning, C. Ronald Kahn, Rohit N. Kulkarni, and Allison B. Goldfine. 2012. Insulin augmentation of glucose-stimulated insulin secretion is impaired in insulin-resistant humans. Diabetes 61(2): 301-309.0012-1797http://nrs.harvard.edu/urn-3:HUL.InstRepos:11235653Type 2 diabetes (T2D) is characterized by insulin resistance and pancreatic β-cell dysfunction, the latter possibly caused by a defect in insulin signaling in β-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 compared with insulin-sensitive subjects, 10 participants with impaired glucose tolerance (IGT), 11 with T2D, and 8 healthy control subjects were studied on two occasions. The insulin secretory 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 augmented GSIS in healthy persons. This effect was attenuated in insulin-resistant cohorts, both those with IGT and those with T2D. Insulin potentiates glucose-stimulated insulin secretion in insulin-resistant subjects to a lesser degree than in normal subjects. This is consistent with an effect of insulin to regulate β-cell function in humans in vivo with therapeutic implications.en-USJournal Article2013-10-2910.2337/db11-1067