β-Cell Deficit in Obese Type 2 Diabetes, a Minor Role of β-Cell Dedifferentiation and Degranulation

J Clin Endocrinol Metab. 2016 Feb;101(2):523-32. doi: 10.1210/jc.2015-3566. Epub 2015 Dec 23.

Abstract

Context: Type 2 diabetes is characterized by a β-cell deficit and a progressive defect in β-cell function. It has been proposed that the deficit in β-cells may be due to β-cell degranulation and transdifferentiation to other endocrine cell types.

Objective: The objective of the study was to establish the potential impact of β-cell dedifferentiation and transdifferentiation on β-cell deficit in type 2 diabetes and to consider the alternative that cells with an incomplete identity may be newly forming rather than dedifferentiated.

Design, setting, and participants: Pancreata obtained at autopsy were evaluated from 14 nondiabetic and 13 type 2 diabetic individuals, from four fetal cases, and from 10 neonatal cases.

Results: Whereas there was a slight increase in islet endocrine cells expressing no hormone in type 2 diabetes (0.11 ± 0.03 cells/islet vs 0.03 ± 0.01 cells/islet, P < .01), the impact on the β-cell deficit would be minimal. Furthermore, we established that the deficit in β-cells per islet cannot be accounted for by an increase in other endocrine cell types. The distribution of hormone negative endocrine cells in type 2 diabetes (most abundant in cells scattered in the exocrine pancreas) mirrors that in developing (embryo and neonatal) pancreas, implying that these may represent newly forming cells.

Conclusions: Therefore, although we concur that in type 2 diabetes there are endocrine cells with altered cell identity, this process does not account for the deficit in β-cells in type 2 diabetes but may reflect, in part, attempted β-cell regeneration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aged
  • Autopsy
  • Body Mass Index
  • Cell Dedifferentiation
  • Cell Degranulation
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / pathology*
  • Humans
  • Infant, Newborn
  • Insulin-Secreting Cells / pathology*
  • Middle Aged
  • Obesity / complications
  • Obesity / pathology*
  • Pancreas / pathology