Insulin augmentation of glucose-stimulated insulin secretion is impaired in insulin-resistant humans

Florencia Halperin, Ximena Lopez, Raquel Manning, C. Ronald Kahn, Rohit N. Kulkarni, Allison B. Goldfine

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Type 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 insulinresistant 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 b-cell function in humans in vivo with therapeutic implications.

Original languageEnglish (US)
Pages (from-to)301-309
Number of pages9
JournalDiabetes
Volume61
Issue number2
DOIs
StatePublished - Feb 1 2012

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Halperin, F., Lopez, X., Manning, R., Kahn, C. R., Kulkarni, R. N., & Goldfine, A. B. (2012). Insulin augmentation of glucose-stimulated insulin secretion is impaired in insulin-resistant humans. Diabetes, 61(2), 301-309. https://doi.org/10.2337/db11-1067