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

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 P4Hα1, 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.