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Biochem Pharmacol. 2011 Feb 15;81(4):471-7. doi: 10.1016/j.bcp.2010.11.010. Epub 2010 Nov 25.

Implications of genome wide association studies for the understanding of type 2 diabetes pathophysiology.

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  • 1BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G11 6TA, United Kingdom.


The rapid rise in prevalence of type 2 diabetes mellitus (T2DM) has been driven by changes in environmental factors - primarily increased caloric intake and reduced energy expenditure - resulting in reduced whole body insulin sensitivity (often termed insulin resistance). Insulin resistance has been proposed to be a major driver of progression to T2DM. However, of 38 individual susceptibility loci for T2DM recently identified by genome wide association studies, by far the majority code for proteins involved in β-cell function. In this review, we discuss the possible reasons for the paucity of insulin resistance genes and ask whether the new genetic susceptibility data should focus attention on β-cell targets in the development of therapies for T2DM.

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