Literature DB >> 18640395

Beta-cell alpha-ketoglutarate hydroxylases may acutely participate in insulin secretion.

Michael J Fallon1, Michael J MacDonald.   

Abstract

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.

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Year:  2008        PMID: 18640395      PMCID: PMC2585369          DOI: 10.1016/j.metabol.2008.03.022

Source DB:  PubMed          Journal:  Metabolism        ISSN: 0026-0495            Impact factor:   8.694


  29 in total

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