Beta-cell alpha-ketoglutarate hydroxylases may acutely participate in insulin secretion.
The presence of Fe(II) alpha-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 P4Halpha1, 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 alpha-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 alpha-ketoglutarate hydroxylases in insulin secretion. It is possible that an increase in mitochondrially generated alpha-ketoglutarate derived from insulin secretagogue carbon and translocated to the cytosol may be part of the signal for insulin secretion.
Fallon
Michael J
MJ
Childrens Diabetes Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.
MacDonald
Michael J
MJ
D000818:Animals; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005971:Glutamates / Q000378:metabolism*; D006801:Humans; D062385:Hydroxybenzoates / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000201:enzymology* / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011393:Procollagen-Proline Dioxygenase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
D004791:Enzyme Inhibitors; D005971:Glutamates; D062385:Hydroxybenzoates; D007328:Insulin; C088956:alpha-ketoglutamic acid; C018063:ethyl protocatechuate; D006899:Mixed Function Oxygenases; D011393:Procollagen-Proline Dioxygenase