The effects of the adipocyte-secreted proteins resistin and visfatin on the pancreatic beta-cell

2.50
Hdl Handle:
http://hdl.handle.net/2436/89148
Title:
The effects of the adipocyte-secreted proteins resistin and visfatin on the pancreatic beta-cell
Authors:
Onyango, David J.
Abstract:
Adipose tissue secreted proteins (adipokines) have been proposed to form a link between obesity and type 2 diabetes (T2D). Resistin and visfatin are two adipokines which have been previously suggested as having roles in the pancreatic islet. The aim of this study was therefore to investigate the regulatory role of the adipokines resistin and visfatin in the pancreatic beta-cell. In order to do this, pancreatic β-cell lines from rat (BRIN-BD11) and mouse (βTC-6) were used to study the effect of exogenous incubation with physiological and pathological concentrations of resistin and visfatin on diverse elements of beta-cell biology including cell viability, gene expression and insulin secretion. In addition to this the expression levels of these two adipokines was also measured in the beta-cell. PCR array analysis showed that resistin and visfatin treatment resulted in significant changes in the expression of key beta-cell specific genes. Interestingly, both resistin and visfatin are highly expressed in the beta-cells. This suggests that the roles of these adipokines are not confined to adipose tissue but also in other endocrine organs. Resistin treatment significantly increased viability of the beta-cells at physiological concentrations however there was no increase with the elevated pathological concentrations. Resistin at elevated concentrations decreased insulin receptor expression in the beta-cells however there was no significant effect at lower concentrations. Both physiological and elevated resistin concentrations did not have any effect on glucose stimulated insulin secretion. Incubation of visfatin induced phosphorylation of insulin receptor and the intracellular signalling MAPK, ERK1/2. Visfatin treatment at 200ng/ml also significantly increased insulin secretion. These effects were replicated by incubation of beta-cells with the product of visfatin’s enzymatic action, nicotinamide mononucleotide and were reversed by visfatin inhibitor FK866. Visfatin treatment at low concentrations did not have any effect on cell viability however the elevated concentrations resulted in a decline. These data indicate that both resistin and visfatin potentially play important roles in beta-cell function and viability and that they form a significant link between adipose tissue and the pancreatic islet in type 2 diabetes.
Advisors:
Dunmore, Simon J.
Publisher:
University of Wolverhampton
Issue Date:
2009
URI:
http://hdl.handle.net/2436/89148
Type:
Thesis or dissertation
Language:
en
Description:
A thesis submitted in partial fulfilment of the requirements of the University of Wolverhampton for degree of Doctor of Philosophy
Appears in Collections:
E-Theses

Full metadata record

DC FieldValue Language
dc.contributor.advisorDunmore, Simon J.en
dc.contributor.authorOnyango, David J.en
dc.date.accessioned2010-01-11T14:13:56Z-
dc.date.available2010-01-11T14:13:56Z-
dc.date.issued2009-
dc.identifier.urihttp://hdl.handle.net/2436/89148-
dc.descriptionA thesis submitted in partial fulfilment of the requirements of the University of Wolverhampton for degree of Doctor of Philosophyen
dc.description.abstractAdipose tissue secreted proteins (adipokines) have been proposed to form a link between obesity and type 2 diabetes (T2D). Resistin and visfatin are two adipokines which have been previously suggested as having roles in the pancreatic islet. The aim of this study was therefore to investigate the regulatory role of the adipokines resistin and visfatin in the pancreatic beta-cell. In order to do this, pancreatic β-cell lines from rat (BRIN-BD11) and mouse (βTC-6) were used to study the effect of exogenous incubation with physiological and pathological concentrations of resistin and visfatin on diverse elements of beta-cell biology including cell viability, gene expression and insulin secretion. In addition to this the expression levels of these two adipokines was also measured in the beta-cell. PCR array analysis showed that resistin and visfatin treatment resulted in significant changes in the expression of key beta-cell specific genes. Interestingly, both resistin and visfatin are highly expressed in the beta-cells. This suggests that the roles of these adipokines are not confined to adipose tissue but also in other endocrine organs. Resistin treatment significantly increased viability of the beta-cells at physiological concentrations however there was no increase with the elevated pathological concentrations. Resistin at elevated concentrations decreased insulin receptor expression in the beta-cells however there was no significant effect at lower concentrations. Both physiological and elevated resistin concentrations did not have any effect on glucose stimulated insulin secretion. Incubation of visfatin induced phosphorylation of insulin receptor and the intracellular signalling MAPK, ERK1/2. Visfatin treatment at 200ng/ml also significantly increased insulin secretion. These effects were replicated by incubation of beta-cells with the product of visfatin’s enzymatic action, nicotinamide mononucleotide and were reversed by visfatin inhibitor FK866. Visfatin treatment at low concentrations did not have any effect on cell viability however the elevated concentrations resulted in a decline. These data indicate that both resistin and visfatin potentially play important roles in beta-cell function and viability and that they form a significant link between adipose tissue and the pancreatic islet in type 2 diabetes.en
dc.language.isoenen
dc.publisherUniversity of Wolverhamptonen
dc.subjectResistinen
dc.subjectVisfatinen
dc.subjectAdipokineen
dc.subjectAdipocyteen
dc.subjectBeta cellen
dc.subjectNampten
dc.subjectDiabetesen
dc.subjectObesityen
dc.subjectInsulinen
dc.subjectPBEFen
dc.titleThe effects of the adipocyte-secreted proteins resistin and visfatin on the pancreatic beta-cellen
dc.typeThesis or dissertationen
dc.type.qualificationnamePhDen
dc.type.qualificationlevelDoctoralen
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