Visfatin regulates insulin secretion, insulin receptor signalling and mRNA expression of diabetes-related genes in mouse pancreatic β-cells

Abstract

The role of the adipocyte-derived factor visfatin in metabolism remains controversial, although some pancreatic b-cellspecific effects have been reported. This study investigated the effects of visfatin upon insulin secretion, insulin receptor activation and mRNA expression of key diabetes-related genes in clonal mouse pancreatic b-cells. b-TC6 cells were cultured in RPMI 1640 and were subsequently treated with recombinant visfatin. One-hour static insulin secretion was measured by ELISA. Phospho-specific ELISA and western blotting were used to detect insulin receptor activation. Real-time SYBR Green PCR array technology was used to measure the expression of 84 diabetes-related genes in both treatment and control cells. Incubation with visfatin caused significant changes in the mRNA expression of several key diabetes-related genes, including marked up-regulation of insulin (9-fold increase), hepatocyte nuclear factor (HNF)1b (32-fold increase), HNF4a (16-fold increase) and nuclear factor kB (40-fold increase). Significant down-regulation was seen in angiotensin-converting enzyme (K3 . 73-fold) and UCP2 (K1 . 3-fold). Visfatin also caused a significant 46% increase in insulin secretion compared to control (P!0 . 003) at low glucose, and this increase was blocked by co-incubation with the specific nicotinamide phosphoribosyltransferase inhibitor FK866. Both visfatin and nicotinamide mononucleotide induced activation of both insulin receptor and extracellular signal-regulated kinase (ERK)1/2, with visfatin-induced insulin receptor/ERK1/2 activation being inhibited by FK866. We conclude that visfatin can significantly regulate insulin secretion, insulin receptor phosphorylation and intracellular signalling and the expression of a number of b-cell function-associated genes in mouse b-cells.

Omentin-1, visfatin and adiponectin levels in relation to bone mineral density in Iranian postmenopausal women

“…However, its operative molecular mechanism is not fully elucidated [35]. Visfatin regulates insulin secretion, insulin receptor signaling, and mRNA expression of diabetes-related genes in mouse pancreatic beta-cells [36]. Visfatin (NAMPT)-mediated systemic nicotinamide adenine dinucleotide (NAD) biosynthesis could alter the enzymatic activities of NAD-dependent deacetylase Sirt1 and affect important metabolic pathways that are essential for regulating glucose-stimulated insulin secretion in pancreatic beta cells [37].…”

Serum visfatin and vaspin levels in normoglycemic first-degree relatives of Iranian patients with type 2 diabetes mellitus

“…Visfatin shows some insulin mimetic properties [24], and its molecular mechanism of actions is under vigorous challenge [4,24,25]. Recently, Brown et al [26] suggested that visfatin can significantly regulate insulin secretion, insulin receptor phosphorylation, and intracellular signaling and expression of a number of beta cell function-associated genes in mouse beta cells.…”

Differences in plasma apelin and visfatin levels between patients with type 1 diabetes mellitus and healthy subjects and response after acute hyperglycemia and insulin administration

“…5 Moreover, it seems to be involved in the regulation of insulin secretion and receptor signaling. 17 Plasma visfatin concentration correlates strongly with the amount of visceral fat. 5 Data on mice have shown that plasma levels of this adipokine increase in the obese state and in mice consuming high fat diet.…”