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

2.50
Hdl Handle:
http://hdl.handle.net/2436/113828
Title:
Visfatin regulates insulin secretion, insulin receptor signalling and mRNA expression of diabetes-related genes in mouse pancreatic beta-cells.
Authors:
Brown, James E. P.; Onyango, David J.; Ramanjaneya, Manjunath; Conner, Alex C.; Patel, Snehal T.; Dunmore, Simon J.; Randeva, Harpal S.
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.
Citation:
Journal of molecular endocrinology, 44 (3):171-178
Publisher:
Society for Endocinology
Journal:
Journal of molecular endocrinology
Issue Date:
2010
URI:
http://hdl.handle.net/2436/113828
DOI:
10.1677/JME-09-0071
PubMed ID:
19906834
Type:
Article
Language:
en
ISSN:
1479-6813
Appears in Collections:
Diabetes, Physiology and Molecular Medicine Research Group

Full metadata record

DC FieldValue Language
dc.contributor.authorBrown, James E. P.en
dc.contributor.authorOnyango, David J.en
dc.contributor.authorRamanjaneya, Manjunathen
dc.contributor.authorConner, Alex C.en
dc.contributor.authorPatel, Snehal T.en
dc.contributor.authorDunmore, Simon J.en
dc.contributor.authorRandeva, Harpal S.en
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):171-178en
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.en
dc.language.isoenen
dc.publisherSociety for Endocinologyen
dc.subject.meshAnimalsen
dc.subject.meshCell Lineen
dc.subject.meshDiabetes Mellitusen
dc.subject.meshInsulinen
dc.subject.meshInsulin-Secreting Cellsen
dc.subject.meshMiceen
dc.subject.meshMitogen-Activated Protein Kinase 1en
dc.subject.meshMitogen-Activated Protein Kinase 3en
dc.subject.meshNicotinamide Phosphoribosyltransferaseen
dc.subject.meshPolymerase Chain Reactionen
dc.subject.meshRNA, Messengeren
dc.subject.meshReceptor, Insulinen
dc.subject.meshSignal Transductionen
dc.titleVisfatin regulates insulin secretion, insulin receptor signalling and mRNA expression of diabetes-related genes in mouse pancreatic beta-cells.en
dc.typeArticleen
dc.identifier.journalJournal of molecular endocrinologyen

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