title: Mitochondrial diabetes mellitus--glucose-induced signaling defects and beta-cell loss.
abstract: 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.
authors.affiliation: Third Department of Internal Medicine, University of Yamaguchi School of Medicine, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Oka
authors.forename: H
authors.initials: H
authors.lastname: Katagiri
authors.forename: H
authors.initials: H
authors.lastname: Ishihara
authors.forename: T
authors.initials: T
authors.lastname: Asano
authors.forename: M
authors.initials: M
authors.lastname: Kikuchi
authors.forename: T
authors.initials: T
authors.lastname: Kobayashi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D004272:DNA, Mitochondrial / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000502:physiology*; D006319:Hearing Loss, Sensorineural / Q000150:complications / Q000235:genetics; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D011446:Prospective Studies
chemical_list: D004272:DNA, Mitochondrial; D007004:Hypoglycemic Agents; D005947:Glucose