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Mitochondrial function in normal and diabetic β-cells

Nature volume 414, pages 807–812 (2001)Cite this article

Abstract

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 β-cell dysfunction caused by mutations in mitochondrial DNA, which is distinct from the nuclear genome. The impact of such mutations on β-cell function reflects the importance of mitochondria in the control of insulin secretion. The β-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.

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Figure 1: A map of human mitochondrial DNA indicating diabetes-associated mutations.
Figure 2: The TCA cycle and respiratory chain in a mitochondrion.
Figure 3: Model for coupling of glucose metabolism to insulin secretion in the β-cell.
Figure 4: Electron micrograph of part of a rat β-cell showing mitochondria (m) and insulin-containing secretory granules (sg).

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Acknowledgements

We apologize to colleagues whose papers were not cited owing to space limitations. We are grateful to L. Orci for kindly providing the Fig. 4, to T. Pozzan and P. Antinozzi for most helpful discussions and to the Swiss National Science Foundation for continued support of our research.

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  1. Division of Clinical Biochemistry, Department of Internal Medicine, University Medical Centre, 1211 Geneva 4, Switzerland

    Pierre Maechler & Claes B. Wollheim

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Correspondence to Pierre Maechler or Claes B. Wollheim.

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Maechler, P., Wollheim, C. Mitochondrial function in normal and diabetic β-cells. Nature 414, 807–812 (2001). https://doi.org/10.1038/414807a

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