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Transcription factors in the pathophysiology of diabetes mellitus

Transcription factors are nuclear proteins which regulate gene expression by enhancing or suppressing transcription of the gene to message RNA, which then is used for translation into the protein for which the gene codes. Recent research has led to the appreciation of the role of transcription factors in the pathophysiology of diabetes mellitus. Genome-wide search (genome mapping and linkage analyis) and examination of candidate genes have led to the identification of genes associated with maturity onset diabetes of the young (MODY). MODY, a disease which is inherited in an autosomal dominant fashion and is characterized by a defect in insulin secretion, is now further subdivided into three groups. MODY2 (1) is linked to mutations in the glucokinase gene, the glucose sensor of the β-cell, while MODY1 (2) and MODY3 (3) are linked to mutations of the transcription factors of hepatocyte nuclear factor (HNF)-la and HNF-4a respectively. HNF-1 and -4, originally