Rat islet mitochondrial adenine nucleotide translocase and the regulation of insulin secretion.

Employing a preparation of rat islet mitochondria, phosphoenolpyruvate has been shown to interact with the mitochondrial adenine nucleotide translocase. Thus, phosphoenolpyruvate inhibited mitochondrial uptake of [14C]ADP and exchanged with intramitochondrial [14C]ATP. A concentration-dependent inhibition of islet mitochondrial 45Ca2+ accumulation was seen when mitochondria were exposed to phosphoenolpyruvate with half-maximal inhibition observed at a phosphoenolpyruvate concentration of 0.2 mM. In experiments employing whole islets, phosphoenolpyruvate content was shown to be significantly elevated at both 1 and 30 min after an increase in the medium glucose concentration from 2 to 20 mM. In these experiments, the estimated islet concentrations of phosphoenolpyruvate fell in the range of maximal sensitivity of the islet adenine nucleotide translocase to phosphoenolpyruvate-induced inhibition of Ca2+ accumulation. It is concluded that increased concentrations of islet phosphoenolpyruvate resulting from increased extracellular glucose concentration may act to trigger or promote glucose-stimulated insulin secretion by modifying the distribution of Ca2+ between the islet cytosolic and mitochondrial compartments in a transport reaction catalyzed by the adenine nucleotide translocase.