Abstract |
The disease maturity-onset diabetes of the young ( MODY) is a genetically heterogeneous monogenic form of non- insulin-dependent ( type 2) diabetes mellitus ( NIDDM), characterized by early onset, usually before 25 years of age and often in adolescence or childhood, and by autosomal dominant inheritance. It has been estimated that 2-5% of patients with NIDDM may have this form of diabetes mellitus. Clinical studies have shown that prediabetic MODY subjects have normal insulin sensitivity but suffer from a defect in glucose-stimulated insulin secretion, suggesting that pancreatic beta-cell dysfunction rather than insulin resistance is the primary defect in this disorder. Linkage studies have localized the genes that are mutated in MODY on human chromosomes 20 ( MODY1), 7 ( MODY2) and 12 ( MODY3), with MODY2 and MODY3 being allelic with the genes encoding glucokinase, a key regulator of insulin secretion, and hepatocyte nuclear factor-1alpha (HNF-1alpha), a transcription factor involved in tissue-specific regulation of liver genes but also expressed in pancreatic islets, insulinoma cells and other tissues. Here we show that MODY1 is the gene encoding HNF-4alpha (gene symbol, TCF14), a member of the steroid/ thyroid hormone receptor superfamily and an upstream regulator of HNF-1alpha expression.
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Authors | K Yamagata, H Furuta, N Oda, P J Kaisaki, S Menzel, N J Cox, S S Fajans, S Signorini, M Stoffel, G I Bell |
Journal | Nature
(Nature)
Vol. 384
Issue 6608
Pg. 458-60
(Dec 05 1996)
ISSN: 0028-0836 [Print] England |
PMID | 8945471
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
- DNA-Binding Proteins
- HNF1A protein, human
- HNF1B protein, human
- HNF4A protein, human
- Hepatocyte Nuclear Factor 1-alpha
- Hepatocyte Nuclear Factor 4
- MLX protein, human
- Nuclear Proteins
- Phosphoproteins
- Receptors, Glucocorticoid
- Transcription Factors
- Hepatocyte Nuclear Factor 1
- Hepatocyte Nuclear Factor 1-beta
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Topics |
- Adult
- Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
- DNA-Binding Proteins
- Diabetes Mellitus, Type 2
(genetics)
- Exons
- Female
- Gene Expression Regulation
- Hepatocyte Nuclear Factor 1
- Hepatocyte Nuclear Factor 1-alpha
- Hepatocyte Nuclear Factor 1-beta
- Hepatocyte Nuclear Factor 4
- Humans
- Male
- Middle Aged
- Molecular Sequence Data
- Mutation
- Nuclear Proteins
- Pedigree
- Phosphoproteins
(genetics)
- Receptors, Glucocorticoid
(genetics)
- Transcription Factors
(genetics)
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