title: Visfatin regulates insulin secretion, insulin receptor signalling and mRNA expression of diabetes-related genes in mouse pancreatic beta-cells.
abstract: The role of the adipocyte-derived factor visfatin in metabolism remains controversial, although some pancreatic beta-cell-specific 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 beta-cells. beta-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)1beta (32-fold increase), HNF4alpha (16-fold increase) and nuclear factor kappaB (40-fold increase). Significant down-regulation was seen in angiotensin-converting enzyme (-3.73-fold) and UCP2 (-1.3-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 beta-cell function-associated genes in mouse beta-cells.
authors.affiliation: School of Life and Health Sciences, Aston Research Centre for Healthy Ageing, Aston University, Birmingham B4 7ET, UK.
authors.forename: James E P
authors.initials: JE
authors.lastname: Brown
authors.forename: David J
authors.initials: DJ
authors.lastname: Onyango
authors.forename: Manjunath
authors.initials: M
authors.lastname: Ramanjaneya
authors.forename: Alex C
authors.initials: AC
authors.lastname: Conner
authors.forename: Snehal T
authors.initials: ST
authors.lastname: Patel
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Dunmore
authors.forename: Harpal S
authors.initials: HS
authors.lastname: Randeva
mesh_terms: D000818:Animals; D002460:Cell Line; D003920:Diabetes Mellitus / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D054409:Nicotinamide Phosphoribosyltransferase / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics*; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics
chemical_list: D007328:Insulin; D012333:RNA, Messenger; D054409:Nicotinamide Phosphoribosyltransferase; D011972:Receptor, Insulin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3