β-Cell Glucose Sensitivity Is Linked to Insulin/Glucagon Bihormonal Cells in Nondiabetic Humans

J Clin Endocrinol Metab. 2016 Feb;101(2):470-5. doi: 10.1210/jc.2015-2802. Epub 2015 Dec 9.

Abstract

Context: Insulin resistance impacts virtually all tissues, including pancreatic β cells. Individuals with insulin resistance, but without diabetes, exhibit an increased islet size because of an elevated number of both β and α cells. Neogenesis from duct cells and transdifferentiation of α cells have been postulated to contribute to the β-cell compensatory response to insulin resistance.

Objective: Our objective was to explore parameters that could potentially predict altered islet morphology.

Methods: We investigated 16 nondiabetic subjects by a 2-hour hyperglycemic clamp to evaluate β-cell secretory function. We analyzed pancreas samples obtained during pancreatoduodenectomy in the same patients to examine glucagon and insulin double+ cells to assess islet morphology.

Results: Among all the functional in vivo parameters of insulin secretion that were explored (basal, first phase and total secretion, glucose sensitivity, arginine-stimulated insulin secretion), β-cell glucose sensitivity was unique in exhibiting a significant correlation with both islet size and α-β double+ islet cells.

Conclusions: Our data suggest that poor β-cell glucose sensitivity is linked to islet transdifferentiation, possibly from α cells to β cells, in an attempt to cope with higher demands for insulin secretion. Understanding the mechanism(s) that underlies the adaptive response of the islet cells to insulin resistance is a potential approach to design tools to enhance functional β-cell mass for diabetes therapy.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Female
  • Glucagon / metabolism*
  • Glucose / pharmacology*
  • Glucose Clamp Technique
  • Humans
  • Hyperglycemia / blood
  • Hyperinsulinism / blood
  • Insulin / metabolism*
  • Insulin-Secreting Cells / drug effects*
  • Islets of Langerhans / anatomy & histology
  • Islets of Langerhans / cytology
  • Male
  • Middle Aged
  • Pancreas / cytology*
  • Pancreas / drug effects
  • Pancreas / metabolism*
  • Pancreatic Ducts / cytology
  • Pancreatic Ducts / metabolism
  • Pancreatic Function Tests
  • Pancreaticoduodenectomy

Substances

  • Insulin
  • Glucagon
  • Glucose