Mitochondrial diabetes mellitus--glucose-induced signaling defects and beta-cell loss

Muscle Nerve Suppl. 1995;3:S131-6. doi: 10.1002/mus.880181426.


Japanese diabetic patients whose mothers were also diabetic were screened, using peripheral leukocytes, for an A to G transition at nucleotide pair 3243 of the mitochondrial gene, a tRNA(Leu)(UUR) mutation. This mutation was identified in four pedigrees from among 300 unrelated patients. Diabetes mellitus cosegretated with the mutation, except in 1 young subject, and was maternally inherited. Long-term follow-up revealed that the underlying disorder in affected members is a progressive impairment of insulin secretion. In accord with this finding, this mutation was found to be highly prevalent in a subset of diabetes mellitus called slowly progressive IDDM; the mutation was identified in 3 of 27 Japanese patients enrolled in the prospective study of islet cell antibody (ICA)-positive, initially non-insulin-dependent diabetic patients, who are very likely to become insulin dependent in several years. The histologic characteristics of slowly progressive IDDM include loss, though incomplete, of pancreatic beta-cells. Mitochondrial gene defects in beta-cells could therefore cause glucose-induced signaling defects as well as beta-cell loss, which explains the wide range of diabetic phenotypes, from NIDDM phenotype to IDDM, in patients with this mitochondrial gene mutation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Base Sequence
  • DNA, Mitochondrial / genetics*
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / metabolism
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / metabolism
  • Female
  • Glucose / physiology*
  • Hearing Loss, Sensorineural / complications
  • Hearing Loss, Sensorineural / genetics
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Islets of Langerhans / metabolism*
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation
  • Prospective Studies


  • DNA, Mitochondrial
  • Hypoglycemic Agents
  • Glucose