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

Teresa Mezza, Gianpio Sorice, Caterina Conte, Vinsin Alice Sun, Chiara Maria Assunta Cefalo, Simona Moffa, Alfredo Pontecorvi, Andrea Mari, Rohit N. Kulkarni, Andrea Giaccari

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)470-475
Number of pages6
JournalTHE JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
Volume101
DOIs
Publication statusPublished - 2016

Keywords

  • insulin resistance
  • trans-differentiation
  • β-cell glucose sensitivity

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