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Human Molecular Genetics Advance Access originally published online on January 20, 2004
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Human Molecular Genetics, 2004, Vol. 13, Review Issue 1 R21-R31
DOI: 10.1093/hmg/ddh066

Type 2 diabetes mellitus: not quite exciting enough?

Frances Ashcroft1,* and Patrik Rorsman2

1University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, UK and 2Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford OX3 7LJ, UK

Type 2 diabetes mellitus is a serious metabolic disease that afflicts around 5% of the population in Western societies and over 150 million people worldwide. It is characterized by elevation of the blood glucose concentration, usually presents in middle age, and is exacerbated by obesity. Both genetic and environmental factors contribute to the disease but in the vast majority of cases the aetiology is still not understood. Here we present a novel hypothesis for the aetiology of type 2 diabetes. We postulate that the electrical activity of the insulin-secreting ß-cells of the pancreas acts to integrate the genetic and environmental factors that predispose to disease risk. Our hypothesis is supported by a substantial amount of data gathered from a range of different disciplines and makes predictions that can be tested experimentally both in vitro and in man.

* To whom correspondence should be addressed. Tel: +44 01865285810; Fax: +44 01865285812; Email: frances.ashcroft{at}physiol.ox.ac.uk


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