Autocrine Effects of Visfatin on Hepatocyte Sensitivity to Insulin Action

Abstract

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.

Effectiveness of Nicotinamide Phosphoribosyltransferase/Pre-B Cell Colony-enhancing Factor/ Visfatin in preventing High Glucose-induced Neurotoxicity in an In-vitro Model of Diabetic Neuropathy

“…Besides, researchers have shown that it has an impact on the immune and vascular system (Erfani et al, 2015, Skop et al, 2009. The neuroprotective effect of visfatin was reported by some researchers.…”

“…Fukuhara et al (2005) introduced visfatin as a new adipokine. At first, it was recognized as nicotinamide phosphoribosyltransferase (Nampt) synthetase and then rediscovered as a pre-B cell colony-enhancing factor (PBEF) that induce the formation of pre-B cell colony (Skop et al, 2009).…”

Association of Diabetes Mellitus and Thyroid Disorders: An Adipocytokines Prospective

“…Visfatin normalized after 6 months of bariatric surgery and consequent weight loss [106]. Visfatin may play an important role in regulating insulin sensitivity in the liver [107]. Visfatin binds to the insulin receptor at a site distinct from insulin and exerts hypoglycemic effect by reducing glucose release from hepatocytes and stimulating glucose utilization in the peripheral tissues [108].…”

Effect of Laparoscopic Sleeve Gastrectomy (LSG) Surgery on Weight Reduction and Serum Visfatin, Ghrelin and Leptin Levels in Morbidly Obese Subjects

“…visfatin actions can be endocrine, paracrine, and autocrine as well. These autocrine effects of visfatin may play an important role in regulating insulin sensitivity in the liver [10]. concentrations of visfatin are increased by hyperglycaemia and lowered HDL-cholesterol level [11], also visfatin plays a pivotal role as regulator of cell energy balance [12].…”