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45Ca2+-accumulation by a mitochondrial fraction from isolated rat pancreatic islets was stronly stimulated by ATP. The ATP-dependent uptake was inhibited by phosphoenolpyruvate in a dose-dependent manner over a wide variety of conditions. Inhibition by phosphoenolpyruvate was non-completitive with respect to calcium, competitive with respect to magnesium, and antagonised by high Mg-ATP2- concentrations; fructose 1,6-diphosphate also decreased 45Ca2+-uptake. Other glucose metabolites were either less effective or ineffective in diminishing mitochondrial 45Ca2+-accumulation. The ATP-dependent uptake was also inhibited by xanthine derivatives (caffeine and 3-isobutyl-1-methylaxanthine) which potentiate the effects of glucose on insulin secretion. Cyclic AMP had no effect. It is thought that the rate of insulin secretion is a function of the cytosolic calcium concentration in the B-cell. These data show that phosphoenolpyruvate, fructose 1,6-diphosphate and methylxanthines might influence exocytosis by direct effects on mitochondrial calcium accumulation, and thus the intracellular distribution of calcium.

diabetologia

Effects of phosphoenolpyruvate, other glycolytic intermediates and methylxanthines on calcium uptake by a mitochondrial fraction from rat pancreatic islets