Hexose metabolism in pancreatic islets. Glucose-induced and Ca(2+)-dependent activation of FAD-glycerophosphate dehydrogenase.
A rise in extracellular D-glucose concentration causes in pancreatic islets a preferential stimulation of aerobic, relative to total, glycolysis. The possible participation in such a phenomenon of a glucose-induced and Ca(2+)-dependent activation of FAD-glycerophosphate dehydrogenase was investigated. In islet homogenates, the activity of the mitochondrial and Ca(2+)-responsive FAD-glycerophosphate dehydrogenase was about two orders of magnitude lower than that of the cytosolic and Ca(2+)-insensitive NAD-glycerophosphate dehydrogenase. In islet mitochondria, Ca2+ increased the affinity of the FAD-glycerophosphate dehydrogenase for L-glycerol 3-phosphate, but did not affect the maximal reaction velocity. In the presence of 0.1 mM-L-glycerol 3-phosphate, the Ka for Ca2+ was close to 0.1 microM. When intact islets were preincubated in the presence of both D-glucose and Ca2+, the activity of FAD-glycerophosphate dehydrogenase measured in intact mitochondria incubated in the presence of 1.2 microM-Ca2+ was higher than that recorded under the same conditions in islets preincubated in the absence of D-glucose and/or Ca2+. These findings support the view that, in islets exposed to a high concentration of D-glucose, a Ca(2+)-induced activation of mitochondrial FAD-glycerophosphate dehydrogenase favours the transfer of reducing equivalents by the glycerol phosphate shuttle, and hence accounts, in part at least, for the preferential stimulation of aerobic glycolysis.
Rasschaert
J
J
Laboratoire de Médecine Expérimentale, Faculté de Médecine, Université Libre de Bruxelles, Belgium.
Malaisse
W J
WJ
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002237:Carbohydrate Dehydrogenases / Q000378:metabolism*; D004789:Enzyme Activation; D005947:Glucose / Q000378:metabolism*; D006601:Hexoses / Q000378:metabolism*; D007515:Islets of Langerhans / Q000201:enzymology / Q000378:metabolism*; D008928:Mitochondria; D051381:Rats
D006601:Hexoses; D002237:Carbohydrate Dehydrogenases; C056470:3-glycerophosphate dehydrogenase; D005947:Glucose; D002118:Calcium