Show simple item record

dc.contributor.authorBrown, James E. P.
dc.contributor.authorOnyango, David J.
dc.contributor.authorRamanjaneya, Manjunath
dc.contributor.authorConner, Alex C.
dc.contributor.authorPatel, Snehal T.
dc.contributor.authorDunmore, Simon J.
dc.contributor.authorRandeva, Harpal S.
dc.date.accessioned2010-10-26T14:14:59Z
dc.date.available2010-10-26T14:14:59Z
dc.date.issued2010
dc.identifier.citationJournal of molecular endocrinology, 44 (3):171-178
dc.identifier.issn1479-6813
dc.identifier.pmid19906834
dc.identifier.doi10.1677/JME-09-0071
dc.identifier.urihttp://hdl.handle.net/2436/113828
dc.description.abstractThe 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.
dc.language.isoen
dc.publisherSociety for Endocinology
dc.subject.meshAnimals
dc.subject.meshCell Line
dc.subject.meshDiabetes Mellitus
dc.subject.meshInsulin
dc.subject.meshInsulin-Secreting Cells
dc.subject.meshMice
dc.subject.meshMitogen-Activated Protein Kinase 1
dc.subject.meshMitogen-Activated Protein Kinase 3
dc.subject.meshNicotinamide Phosphoribosyltransferase
dc.subject.meshPolymerase Chain Reaction
dc.subject.meshRNA, Messenger
dc.subject.meshReceptor, Insulin
dc.subject.meshSignal Transduction
dc.titleVisfatin regulates insulin secretion, insulin receptor signalling and mRNA expression of diabetes-related genes in mouse pancreatic beta-cells.
dc.typeJournal article
dc.identifier.journalJournal of molecular endocrinology
html.description.abstractThe 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.


This item appears in the following Collection(s)

Show simple item record