Dunmore, Simon - University of Wolverhampton - Faculty of Science & Engineering

研究领域

Our current interest is in beta-cell failure in type 2 diabetes. We were the first team worldwide to publish evidence suggesting that UCP-2 may have a role in glucolipotoxicity in the human beta-cell in type 2 diabetes and we have recently amassed and published data on the effects of adipokines (including leptin, adiponectin, resistin and visfatin) on beta-cell function and survival. In addition to our novel finding that hyperglycaemia increases UCP-2 expression in human islets (Brown et al. 2002) and rodent beta-cells (Brown and Dunmore, 2007), and thus may impair GSIS and beta-cell viability by doing so, we have shown that leptin directly inhibits insulin secretion and reduces UCP-2 expression and promotes beta cell survival by inhibiting the apoptotic pathway. We were recently awarded the prestigious Eli Lilly prize at the Diabetes UK Annual Professional Conference 2005 for our presentation of part of this work. More recently we have shown (with Dr H Randeva and Dr J Digby, University of Warwick, paper in preparation) that adiponectin receptor is expressed in beta-cells, predominantly the AdR1 isoform, that AdR expression is differentially modulated by monounsaturated and saturated fatty acids and by PPARa and g agonists, and that adiponectin is able to increase beta-cell viability. Adiponectin also increased LPL (lipoprotein lipase) and decreased PDX-1 expression in beta-cells. We have also shown that resistin inhibits insulin-receptor expression in beta-cells and that this may explain resistin-induction of “insulin resistance” in beta-cells observed by other groups (Brown et al. 2007). Another, recently discovered, adipokine is visfatin and we have demonstrated that this is also regulates gene expression in, and is expressed by, the beta-cell. Other research interests: Cardiovascular disease in diabetes and the role of adipokines (with Dr J Vickers, Diabetes & Metabolic Diseases Group). I have a number of ongoing clinical studies with Professor Rousseau Gama (New Cross Hospital, Wolverhampton) examining biochemical markers of myocardial damage/ischaemia and ethnicity of cardiovascular risk factors (Chatha K et al. 2006a & b) and am also jointly supervising with Dr James Cotton (Consultant Cardiologist, New Cross Hospital) the MD research of a Specialist Registrar into platelet resistance to clopidogrel and aspirin in unstable coronary artery disease.

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Brown JE, Thomas S, Digby JE, Dunmore SJ (2002) Glucose induces and leptin decreases expression of uncoupling protein-2 mRNA in human islets. FEBS Lett 513: 189-92 Seyffarth G, Nelson PN, Dunmore SJ, Rodrigo N, Murphy DJ, Carson RJ (2004) Lipopolysaccharide induces nitric oxide synthase expression and platelet-activating factor increases nitric oxide production in human fetal membranes in culture. Reproductive Biology and Endocrinology 2:29 Brown JEP, Ward KL, Patel D & Dunmore SJ (2005) Regulation of uncoupling protein-2 expression and cell viability in rodent beta-cells by leptin. Diabetic Medicine 22 (s2): 32 (Awarded Eli Lilly Poster Award at Diabetes UK Professional Section conference, Glasgow, April 2005) Chatha K, Alsoud M, Griffiths MJ, Elfatih A, Horton RC, Dunmore SJ, Gama R. (2006) NT-proBNP and exercise. Ann Clin Biochem. 43: 240 Chatha K, Alsoud M, Griffiths MJ, Elfatih A, Abozguia K, Horton RC, Dunmore SJ, Gama R. (2006) B-type natriuretic peptide in reversible myocardial ischaemia. J Clin Pathol. 59:1216-7 Brown JE, Onyango DJ, Dunmore SJ. (2007) Resistin down-regulates insulin receptor expression, and modulates cell viability in rodent pancreatic beta-cells. FEBS Lett. 581:3273-6. Epub 2007 Jun 21. Brown JEP, Dunmore SJ. (2007) Leptin decreases apoptosis and alters BCL-2:Bax ratio in clonal rodent pancreatic beta-cells. Diabetes Metab Res Rev. 23: 497-502