β-Cell α-ketoglutarate hydroxylases may acutely participate in insulin secretion

Abstract

The presence of Fe(II) α-ketoglutarate hydroxylases in rat and human pancreatic islets and INS-1 832/13 cells was demonstrated with the reverse transcriptase polymerase chain reaction (PHD1, 2, and 3; lysyl hydroxylases 1, 2, and 3; and phytanoyl–coenzyme A hydroxylase were seen) and/or immunoblotting (high levels of proline hydroxylase P4H α1, PHD2, and PHD4 and low levels of PHD2 and PHD3 in human islets, and high levels of PHD2 in rat islets and INS-1 cells were seen). Prolyl hydroxylase enzyme activity in INS-1 832/13 cells was purified with polyproline affinity chromatography. Inhibitors of α-ketoglutarate hydroxylases lowered glucose-induced and leucine-plus-glutamine–induced insulin release in rat pancreatic islets, suggesting that there may be acute unknown effects of α-ketoglutarate hydroxylases in insulin secretion. It is possible that an increase in mitochondrially generated α-ketoglutarate derived from insulin secretagogue carbon and translocated to the cytosol may be part of the signal for insulin secretion.