Visfatin was originally described as an adipokine with insulin mimetic effects. Recently, it was found that visfatin is identical with the Nampt (nicotinamide phosphoribosyltransferase) gene that codes for an intra- and extracellular NAD biosynthetic enzyme and is predominantly expressed outside the adipose tissue. In the current study, we found strong protein and mRNA expression of visfatin in rat heart, liver, kidney, and muscle, while the expression of visfatin in visceral fat was significantly lower and undetectable in subcutaneous fat. The insulin-mimetic effects of visfatin (extracellular form of Nampt or eNampt) are controversial and even less is known about autocrine effects of visfatin (intracellular form of Nampt or iNampt). Since liver plays a major role in glucose metabolism, we studied visfatin effects on insulin-stimulated cellular glucose uptake in Fao rat hepatocytes using RNA interference (RNAi). RNAi-mediated downregulation of visfatin expression in Fao cells was associated with significantly reduced NAD biosynthesis (0.3±0.01 vs. 0.5±0.01 mmol/h/g, P<0.05) and with significantly decreased incremental glucose uptake after stimulation with insulin when compared to controls with normal expression of visfatin (0.6±0.2 vs. 2.2±0.5 nnmol/g/2 h, P=0.02). These results provide evidence that visfatin exhibits important autocrine effects on sensitivity of liver cells to insulin action possibly through its effects on NAD biosynthesis.
- MeSH
- autokrinní signalizace MeSH
- biologický transport MeSH
- buněčné linie MeSH
- cytokiny genetika metabolismus MeSH
- financování organizované MeSH
- glukosa metabolismus MeSH
- hepatocyty enzymologie MeSH
- inzulin metabolismus MeSH
- inzulinová rezistence MeSH
- krysa rodu rattus MeSH
- messenger RNA metabolismus MeSH
- NAD metabolismus MeSH
- nikotinamidfosforibosyltransferasa genetika metabolismus MeSH
- potkani inbrední WKY MeSH
- regulace genové exprese enzymů MeSH
- RNA interference MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
It has been suggested that thiazolidinediones (TZDs) ameliorate insulin resistance in muscle tissue by suppressing muscle lipid storage and the activity of novel protein kinase C (nPKC) isoforms. To test this hypothesis, we analyzed long-term metabolic effects of pioglitazone and the activation of nPKC-? and -? isoforms in an animal model of the metabolic syndrome, the spontaneously hypertensive rat (a congenic SHR strain with wild type Cd36 gene) fed a diet with 60 % sucrose from the age of 4 to 8 months. Compared to untreated controls, pioglitazone treatment was associated with significantly increased basal (809±36 vs 527±47 nmol glucose/g/2h, P<0.005) and insulinstimulated glycogenesis (1321±62 vs 749±60 nmol glucose/g/2h, P<0.0001) in isolated gastrocnemius muscles despite increased concentrations of muscle triglycerides (3.83±0.33 vs 2.25±0.12 µmol/g, P<0.005). Pioglitazone-treated rats exhibited significantly increased membrane/total (cytosolic plus membrane) ratio of both PKC-? and PKC-? isoforms compared to untreated controls. These results suggest that amelioration of insulin resistance after long-term pioglitazone treatment is associated with increased activation of PKC-? and -? isoforms in spite of increased lipid concentration in skeletal muscles.
- MeSH
- antigeny CD36 genetika metabolismus MeSH
- časové faktory MeSH
- financování organizované MeSH
- glykogen metabolismus MeSH
- hypoglykemika farmakologie MeSH
- inzulin metabolismus MeSH
- inzulinová rezistence MeSH
- izoenzymy metabolismus MeSH
- konzumní sacharóza aplikace a dávkování metabolismus MeSH
- kosterní svaly enzymologie patofyziologie účinky léků MeSH
- krevní glukóza metabolismus MeSH
- krysa rodu rattus MeSH
- metabolický syndrom MeSH
- modely nemocí na zvířatech MeSH
- potkani inbrední SHR MeSH
- proteinkinasa C metabolismus MeSH
- thiazolidindiony farmakologie MeSH
- transport proteinů MeSH
- triglyceridy metabolismus MeSH
- zvířata kongenní MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
