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Metabolism

Insulin Augmentation of Glucose-Stimulated Insulin Secretion Is Impaired in Insulin-Resistant Humans

  1. Florencia Halperin1,2,3,
  2. Ximena Lopez1,2,4,
  3. Raquel Manning1,
  4. C. Ronald Kahn1,3,
  5. Rohit N. Kulkarni1,3 and
  6. Allison B. Goldfine1,2,3⇓
  1. 1Joslin Diabetes Center, Boston, Massachusetts;
  2. 2Brigham and Women’s Hospital, Boston, Massachusetts;
  3. 3Harvard Medical School, Boston, Massachusetts;
  4. 4University of Texas Southwestern Medical Center, Dallas, Texas
  1. Corresponding author: Allison B. Goldfine, allison.goldfine{at}joslin.harvard.edu.
Diabetes 2012 Feb; 61(2): 301-309. https://doi.org/10.2337/db11-1067
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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 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.

  • Received July 29, 2011.
  • Accepted October 29, 2011.
  • © 2012 by the American Diabetes Association.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

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Diabetes: 61 (2)

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February 2012, 61(2)
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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
Diabetes Feb 2012, 61 (2) 301-309; DOI: 10.2337/db11-1067

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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
Diabetes Feb 2012, 61 (2) 301-309; DOI: 10.2337/db11-1067
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