The role of transcription factors in maturity-onset diabetes of the young

• Published in: Molecular Genetics and Metabolism Vol. 77; no. 1; pp. 35 - 43
• Main Authors: Mitchell, Simon M.S, Frayling, Timothy M
• Format: Book Review Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2002
• Subjects: Alleles; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Basic Helix-Loop-Helix Transcription Factors; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - metabolism; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Gene Expression Regulation; Genetic Variation; Glucokinase - genetics; Glucokinase - metabolism; Hepatocyte Nuclear Factor 1; Hepatocyte Nuclear Factor 1-alpha; Hepatocyte Nuclear Factor 1-beta; Hepatocyte Nuclear Factor 4; Homeodomain Proteins; Humans; Islets of Langerhans - metabolism; Nuclear Proteins; Phenotype; Phosphoproteins - genetics; Phosphoproteins - metabolism; Trans-Activators - genetics; Trans-Activators - metabolism; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 1096-7192; 1096-7206
• DOI: 10.1016/S1096-7192(02)00150-6

The study of maturity-onset diabetes of the young (MODY), an autosomal dominant form of early-onset diabetes mellitus characterised by defective insulin secretion has been extremely successful in two ways. Firstly it has enabled definitive diagnosis for patients. This allows more accurate prediction of disease and treatment requirements. Secondly it has facilitated an increased understanding of the genes and pathways that are crucial for normal β-cell function. Five of the six MODY genes, TCF1 (encoding HNF-1α), TCF2 (encoding HNF-1β) HNF4A, insulin promoter factor (IPF)1, and NEUROD1, are transcription factors that operate in a complex network of gene regulation. Several genes have been shown to be regulated by the MODY transcription factors in a β-cell specific manner. This includes the co-regulation of HNF-1α and HNF-4α by each other. The exact mechanism of how mutations in these transcription factors result in diabetes in humans remains unknown. However, current opinion favours pleiotropic adverse effects on many genes; extensive in vitro and in vivo studies of these genes has highlighted their importance in both glucose sensing—insulin secretion coupling and maintaining the fully differentiated β-cell phenotype.