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- Title
What Couples Glycolysis to Mitochondrial Signal Generation in Glucose-Stimulated Insulin Secretion?
- Authors
Ishihara, Hisamitsu; Wollheim, Claes B.
- Abstract
Pancreatic islet β-cells are poised to generate metabolic messengers in the mitochondria that link glucose metabolism to insulin exocytosis. This is accomplished through the tight coupling of glycolysis to mitochondrial activation. The messenger molecules ATP and glutamate are produced after the metabolism of glycolysis-derived pyruvate in the mitochondria. The entry of monocarboxylates such as pyruvate into the β cell is limited, explaining why overexpression of monocarboxylate transporters unravels pyruvate-stimulated insulin secretion. NADH generated by glycolysis is efficiently reoxidized by highly active mitochondrial shuttles rather than by lactate dehydrogenase. Overexpression of this enzyme does not alter glucose-stimulated insulin secretion, suggesting that NADH availability restricts the conversion of pyruvate to lactate in the β cell. These metabolic features permit the fuel function of glucose to be extended to the generation of signaling molecules, which increases cytosolic Ca[sup 2+] and promotes insulin exocytosis.
- Subjects
PANCREATIC beta cells; GLYCOLYSIS; MITOCHONDRIA; GLUCOSE; NAD(P)H dehydrogenases; BIOCHEMICAL mechanism of action; METABOLISM
- Publication
IUBMB Life, 2000, Vol 49, Issue 5, p391
- ISSN
1521-6543
- Publication type
Article
- DOI
10.1080/152165400410236