β-Cell loss and glucose induced signalling defects in diabetes mellitus caused by mitochondrial tRNA(Leu(UUR)) gene mutation

Y. Oka, H. Katagiri, H. Ishihara, T. Asano, T. Kobayashi, M. Kikuchi

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

Japanese diabetic patients with diabetic mothers were screened, using peripheral leukocytes, for an A to C transition at nucleotide pair 3243, a tRNA(Leu(UUR)) mutation of the mitochondrial gene. This mutation was identified in four pedigrees from among 300 unrelated patients. Diabetes mellitus cosegregated with the mutation, except in one young subject, and was maternally inherited. Long-term follow-up revealed that the underlying disorder, in affected individuals, is a progressive impairment of insulin secretion. In accordance with this finding, the mutation was found to be highly prevalent in a diabetes mellitus subset termed slowly progressive IDDM; the mutation was identified in 3 out of 27 subjects enrolled in the prospective study of islet cell antibody (ICA)-positive, initially non-insulin-dependent diabetic Japanese patients, who are at high risk of progressing to insulin dependence over several years. The histologic characteristics of slowly progressive insulin-dependent diabetes mellitus include substantial loss, though incomplete, of pancreatic β-cells. Mitochondrial gene defects in β-cells could therefore cause glucose-induced signalling defects as well as β-cell loss. This would explain the wide range of diabetic phenotypes, from NIDDM to IDDM, in patients with this mitochondrial gene mutation.

Original languageEnglish
Pages (from-to)S98-S102
JournalDiabetic Medicine
Volume13
Issue numberSUPPL. 6
DOIs
Publication statusPublished - 1996
Externally publishedYes

Keywords

  • Insulin secretory defect
  • Mitochondrial gene mutation
  • Secondary sulphonylurea failure
  • Slowly progressive IDDM
  • β-Cell loss

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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