Prime suspect: the TCF7L2 gene and type 2 diabetes risk.
Transcription factor-7-like 2 (TCF7L2) is the most important type 2 diabetes susceptibility gene identified to date, with common intronic variants strongly associated with diabetes in all major racial groups. This ubiquitous transcription factor in the Wnt signaling pathway was not previously known to be involved in glucose homeostasis, so defining the underlying mechanism(s) will provide new insights into diabetes. In this issue of the JCI, Lyssenko and colleagues report on their human and isolated islet studies and suggest that the risk allele increases TCF7L2 expression in the pancreatic beta cell, reducing insulin secretion and hence predisposing the individual to diabetes (see the related article beginning on page 2155).
Hattersley
Andrew T
AT
Institute of Biomedical and Clinical Sciences, Peninsula Medical School, Exeter, United Kingdom. Andrew.Hattersley@pms.ac.uk
D000328:Adult; D000368:Aged; D000483:Alleles; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005060:Europe; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005947:Glucose / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012307:Risk Factors; D051820:TCF Transcription Factors / Q000235:genetics* / Q000378:metabolism; D058118:Transcription Factor 7-Like 2 Protein
D007328:Insulin; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein; D005947:Glucose