Mitochondrial function in normal and diabetic beta-cells.
The aetiology of type 2, or non-insulin-dependent, diabetes mellitus has been characterized in only a limited number of cases. Among these, mitochondrial diabetes, a rare subform of the disease, is the consequence of pancreatic beta-cell dysfunction caused by mutations in mitochondrial DNA, which is distinct from the nuclear genome. The impact of such mutations on beta-cell function reflects the importance of mitochondria in the control of insulin secretion. The beta-cell mitochondria serve as fuel sensors, generating factors that couple nutrient metabolism to the exocytosis of insulin-containing vesicles. The latter process requires an increase in cytosolic Ca2+, which depends on ATP synthesized by the mitochondria. This organelle also generates other factors, of which glutamate has been proposed as a potential intracellular messenger.
Maechler
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Division of Clinical Biochemistry, Department of Internal Medicine, University Medical Centre, 1211 Geneva 4, Switzerland. pierre.maechler@medecine.unige.ch
Wollheim
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CB
D000818:Animals; D004272:DNA, Mitochondrial; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D005089:Exocytosis; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000502:physiology* / Q000503:physiopathology; D008928:Mitochondria / Q000502:physiology*; D028361:Mitochondrial Diseases / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D009154:Mutation; D015398:Signal Transduction
D004272:DNA, Mitochondrial; D007328:Insulin