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

James Brown, David J. Onyango, Manjunath Ramanjaneya, Alex C. Conner, Snehal T. Patel, Simon J. Dunmore, Harpal S. Randeva

Research output: Contribution to journalArticle

Abstract

The role of the adipocyte-derived factor visfatin in metabolism remains controversial, although some pancreatic ß-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 ß-cells. ß-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)1ß (32-fold increase), HNF4a (16-fold increase) and nuclear factor ?B (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 ß-cell function-associated genes in mouse ß-cells.
LanguageEnglish
Pages171-178
Number of pages9
JournalJournal of Molecular Endocrinology
Volume44
Issue number3
Early online date11 Nov 2009
DOIs
Publication statusPublished - 1 Mar 2010

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Nicotinamide Phosphoribosyltransferase
Insulin Receptor
Insulin-Secreting Cells
Insulin
Messenger RNA
Genes
Nicotinamide Mononucleotide
Enzyme-Linked Immunosorbent Assay
Hepatocyte Nuclear Factors
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Peptidyl-Dipeptidase A
Adipocytes
Cultured Cells
Up-Regulation
Down-Regulation
Cell Count
Western Blotting
Phosphorylation
Technology

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Brown, James ; Onyango, David J. ; Ramanjaneya, Manjunath ; Conner, Alex C. ; Patel, Snehal T. ; Dunmore, Simon J. ; Randeva, Harpal S. / Visfatin regulates insulin secretion, insulin receptor signalling and mRNA expression of diabetes-related genes in mouse pancreatic beta-cells. In: Journal of Molecular Endocrinology. 2010 ; Vol. 44, No. 3. pp. 171-178.
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Visfatin regulates insulin secretion, insulin receptor signalling and mRNA expression of diabetes-related genes in mouse pancreatic beta-cells. / Brown, James; Onyango, David J.; Ramanjaneya, Manjunath; Conner, Alex C.; Patel, Snehal T.; Dunmore, Simon J.; Randeva, Harpal S.

In: Journal of Molecular Endocrinology, Vol. 44, No. 3, 01.03.2010, p. 171-178.

Research output: Contribution to journalArticle

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