Open AccessAutocrine Effects of Visfatin on Hepatocyte Sensitivity to Insulin Action
Author(s) -
Vojtěch Škop,
K. Kontrová,
Václav Zı́dek,
Michal Pravenec,
Ludmila Kazdová,
K. Mikulík,
J. Sajdok,
J. Zídková
Publication year - 2010
Publication title -
physiological research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.647
H-Index - 70
eISSN - 1802-9973
pISSN - 0862-8408
DOI - 10.33549/physiolres.931845
Subject(s) - nicotinamide phosphoribosyltransferase , medicine , endocrinology , autocrine signalling , insulin , adipokine , adipose tissue , nad+ kinase , downregulation and upregulation , chemistry , sirtuin 1 , glucose uptake , carbohydrate metabolism , hepatocyte , extracellular , insulin resistance , biology , enzyme , biochemistry , receptor , in vitro , gene
Visfatin was originally described as an adipokine with insulinmimetic effects. Recently, it was found that visfatin is identicalwith the Nampt (nicotinamide phosphoribosyltransferase) genethat codes for an intra- and extracellular NAD biosyntheticenzyme and is predominantly expressed outside the adiposetissue. In the current study, we found strong protein and mRNAexpression of visfatin in rat heart, liver, kidney, and muscle, whilethe expression of visfatin in visceral fat was significantly lowerand undetectable in subcutaneous fat. The insulin-mimeticeffects of visfatin (extracellular form of Nampt or eNampt) arecontroversial and even less is known about autocrine effects ofvisfatin (intracellular form of Nampt or iNampt). Since liver playsa major role in glucose metabolism, we studied visfatin effects oninsulin-stimulated cellular glucose uptake in Fao rat hepatocytesusing RNA interference (RNAi). RNAi-mediated downregulation ofvisfatin expression in Fao cells was associated with significantlyreduced NAD biosynthesis (0.3±0.01 vs. 0.5±0.01 mmol/h/g,P<0.05) and with significantly decreased incremental glucoseuptake after stimulation with insulin when compared to controlswith normal expression of visfatin (0.6±0.2 vs. 2.2±0.5nnmol/g/2 h, P=0.02). These results provide evidence thatvisfatin exhibits important autocrine effects on sensitivity of livercells to insulin action possibly through its effects on NADbiosynthesis.