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

Abstract

⁴⁵Ca²⁺-accumulation by a mitochondrial fraction from isolated rat pancreatic islets was strongly 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 noncompetitive 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-l-methylxanthine) 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.