Association between polymorphisms of TCF7L2 and type 2 diabetes with special reference to incretin action

: TCF7L2 is a Wnt signaling-associated transcription factor and is ubiquitously expressed. Polymorphisms in the TCF7L2 gene exhibit the strongest association with type 2 diabetes among approximately twenty susceptibility gene variants identified to date. Although the mechanisms by which TCF7L2 affects susceptibility to type 2 diabetes remain to be elucidated, several studies have shown that decreased TCF7L2 protein inhibits the insulin secretory response to oral glucose through impaired incretin action(GLP-1, GIP). In this review, we discuss studies that investigate the association between polymorphisms of TCF7L2 and the diabetic phenotype, especially in vitro beta cell function with special reference to incretin action and the response to lifestyle intervention.