Hexose metabolism in pancreatic islets: regulation of the mitochondrial NADH/NAD+ ratio.
In rat pancreatic islets, D-glucose in concentrations exceeding 5.6 mM caused a concentration-related decrease of the mitochondrial NADH/NAD+ ratio, as judged from the changes in the islet content of glutamate, NH4+, and 2-ketoglutarate, and assuming that the glutamate dehydrogenase reaction is near equilibrium with the mitochondrial NAD system. The concentration dependency of the response to D-glucose was vastly different in islet and parotid cells, respectively. L-Leucine, 2-ketoisocaproate, BCH (a nonmetabolized but insulinotropic analog of L-leucine) and 3-phenylpyruvate also lowered the mitochondrial NADH/NAD+ ratio. In the presence of D-glucose, the latter ratio was also decreased by NH4+ or the absence of extracellular Ca2+, but dramatically increased by aminooxyacetate. Taking into account prior metabolic findings, the nutrient-induced fall in the mitochondrial redox state is thought to reflect an increased clearance of mitochondrial NADH through both the respiratory chain and malate-aspartate shuttle. The nutrient-induced decrease in the mitochondrial NADH/NAD+ ratio might favor both the circulation of metabolites in the Krebs cycle and the exit of Ca2+ from the mitochondria.
Ramirez
R
R
Laboratory of Experimental Medicine, Brussels Free University, Belgium.
Sener
A
A
Malaisse
W J
WJ
D000596:Amino Acids / Q000494:pharmacology; D000598:Amino Acids, Cyclic; D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007651:Keto Acids / Q000494:pharmacology; D007930:Leucine / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009243:NAD / Q000378:metabolism*; D010084:Oxidation-Reduction; D010667:Phenylpyruvic Acids / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D000596:Amino Acids; D000598:Amino Acids, Cyclic; D007651:Keto Acids; D010667:Phenylpyruvic Acids; D000644:Quaternary Ammonium Compounds; D009243:NAD; D000625:Aminooxyacetic Acid; C006504:2-aminobicyclo(2,2,1)heptane-2-carboxylic acid; C013082:alpha-ketoisocaproic acid; D007930:Leucine; D005947:Glucose; D002118:Calcium; C031606:phenylpyruvic acid