Role of NADH shuttle system in glucose-induced activation of mitochondrial metabolism and insulin secretion.
Glucose metabolism in glycolysis and in mitochondria is pivotal to glucose-induced insulin secretion from pancreatic beta 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.
Eto
K
K
Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan. Tokyo,
Tsubamoto
Y
Y
Terauchi
Y
Y
Sugiyama
T
T
Kishimoto
T
T
Takahashi
N
N
Yamauchi
N
N
Kubota
N
N
Murayama
S
S
Aizawa
T
T
Akanuma
Y
Y
Aizawa
S
S
Kasai
H
H
Yazaki
Y
Y
Kadowaki
T
T
D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D001219:Aspartate Aminotransferases / Q000037:antagonists & inhibitors; D002118:Calcium / Q000378:metabolism; D002952:Citric Acid Cycle; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D018390:Gene Targeting; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D005993:Glycerolphosphate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D006019:Glycolysis; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D009243:NAD / Q000378:metabolism*; D019289:Pyruvic Acid / Q000378:metabolism