Mitochondrial function in normal and diabetic beta-cells

The aetiology of type 2, or non-insulin-dependent, diabetes mellitus has be en characterized in only a limited number of cases. Among these, mitochondr ial diabetes, a rare subform of the disease, is the consequence of pancreat ic beta -cell dysfunction caused by mutations in mitochondrial DNA, which i s distinct from the nuclear genome. The impact of such mutations on beta -c ell function reflects the importance of mitochondria in the control of insu lin secretion. The beta -cell mitochondria serve as fuel sensors, generatin g factors that couple nutrient metabolism to the exocytosis of insulin-cont aining 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 potentia l intracellular messenger.