Identifying the mechanism behind a genetic susceptibility to type 2 diabetes
Type 2 diabetes is reaching epidemic proportions in the developed world. Determining if and how certain genes predispose individuals to type 2 diabetes is likely to lead to the development of new treatment strategies for individuals with the disease.
In a study appearing in the August issue of the Journal of Clinical Investigation Valeriya Lyssenko and colleagues from Lund University in Sweden show that certain variants of the gene TCF7L2 make individuals more susceptible to type 2 diabetes. The susceptibility variants were associated with increased expression of TCF7L2 in pancreatic islet cells and decreased islet cell secretion of insulin. Consistent with this, ectopic overexpression of TCF7L2 in human islet cells decreased insulin secretion in response to exposure to glucose. This study identifies TCF7L2 type 2 diabetes susceptibility variants and provides a mechanism by which these genetic variants might cause susceptibility to the disease. As discussed by the authors and in the accompanying commentary by Andrew Hattersley from Peninsula Medical School in the United Kingdom, future studies are likely to investigate the potential for manipulating the signaling pathways controlled by TCF7L2 for the development of new therapeutics for type 2 diabetes.
TITLE: Mechanisms by which common variants in the TCF7L2 gene increase risk of type 2 diabetes
AUTHOR CONTACT:
Valeriya Lyssenko
Lund University, University Hospital Malma, Malma, Sweden.
Phone: 46-40-391214; Fax: 46-40-391222; E-mail: Valeri.Lyssenko@med.lu.se.
View the PDF of this article at: https://www.the-jci.org/article.php?id=30706
ACCOMPANYING COMMENTARY
TITLE: Prime suspect: the TCF7L2 gene and type 2 diabetes risk
AUTHOR CONTACT:
Andrew T. Hattersley
Institute of Biomedical and Clinical Sciences, Peninsula Medical School, Exeter, United Kingdom.
Phone: 44-1392-406806; Fax: 44-1392-406767; E-mail: Andrew.Hattersley@pms.ac.uk.
View the PDF of this article at: https://www.the-jci.org/article.php?id=33077
Journal
Journal of Clinical Investigation