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Role of NADH Shuttle System in Glucose-Induced Activation of Mitochondrial Metabolism and Insulin Secretion

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Science  12 Feb 1999:
Vol. 283, Issue 5404, pp. 981-985
DOI: 10.1126/science.283.5404.981

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Abstract

Glucose metabolism in glycolysis and in mitochondria is pivotal to glucose-induced insulin secretion from pancreatic β cells. One or more factors derived from glycolysis other than pyruvate appear to be required for the generation of mitochondrial signals that lead to insulin secretion. The electrons of the glycolysis-derived reduced form of nicotinamide adenine dinucleotide (NADH) are transferred to mitochondria through the NADH shuttle system. By abolishing the NADH shuttle function, glucose-induced increases in NADH autofluorescence, mitochondrial membrane potential, and adenosine triphosphate content were reduced and glucose-induced insulin secretion was abrogated. The NADH shuttle evidently couples glycolysis with activation of mitochondrial energy metabolism to trigger insulin secretion.

  • * To whom correspondence should be addressed. E-mail: kadowaki-3im{at}h.u-tokyo.ac.jp

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