Molecular and histological evaluation of pancreata from patients with a mitochondrial gene mutation associated with impaired insulin secretion

Biochem Biophys Res Commun. 1999 May 27;259(1):149-56. doi: 10.1006/bbrc.1999.0650.

Abstract

A mutation in mitochondrial DNA, which was originally identified in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), can be associated with a subtype of diabetes mellitus. To determine the molecular and histological basis of impaired insulin secretion in the subjects with this mutation, we studied autopsy pancreata specimens from eight subjects diagnosed as having MELAS. The 3243 bp mutation was identified in seven out of eight pancreata examined. Immunohistochemical studies demonstrated a reduction in total islet mass, and in the numbers of both B and A cells. No evidence of insulitis or apoptosis was found. These data suggested that the 3243 bp mutation may cause the reduction of islet cells, mainly through mechanisms other than autoimmune destruction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • DNA Mutational Analysis
  • DNA, Mitochondrial / genetics*
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 2 / genetics
  • Female
  • Humans
  • Immunohistochemistry
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans / pathology
  • Japan
  • MELAS Syndrome / genetics*
  • Male
  • Middle Aged
  • Mutation*
  • Pancreas / metabolism*
  • Pancreas / pathology
  • Polymerase Chain Reaction

Substances

  • DNA, Mitochondrial
  • Insulin