Overexpression of TCF7L2 reduces insulin secretion in response to glucose.
Scientists from Lund University found how a particular variant of the gene encoding for transcription factor-7–like 2 (TCF7L2) makes individuals more susceptible to type 2 diabetes.
The team followed subjects that were genotyped for three SNPs (rs7903146, rs12255372, and rs10885406) in TCF7L2 for up to 22 years, and a subset of them underwent extensive metabolic studies to determine how the gene influences the formation of the disease.
The rs790314 variant, which strongly predicted type 2 diabetes, was associated with increased expression of TCF7L2 in pancreatic islet cells and decreased islet cell secretion of insulin. Consistent with this, abnormal overexpression of TCF7L2 in human islet cells decreased glucose-activated insulin secretion.
Researchers from the University of Pisa, Helsinki University, and the Folkhälsan Institute of Genetics were also invovled in the study, which appears in the August issue of the Journal of Clinical Investigation.