Author: Kitanaka, Sachiko

Source: Expert Review of Endocrinology and Metabolism, Volume 3, Number 4, July 2008 , pp. 441-452(12)

Publisher: Expert Reviews

Abstract:

Hepatocyte nuclear factor (HNF)-1α and HNF-1β are transcription factors that regulate many target genes in various tissues including liver, pancreas and kidney. Heterozygous mutations in the HNF-1α and HNF-1β genes result in maturity-onset diabetes of the young (MODY)3 and MODY5, respectively. The discovery of these `hepatocyte nuclear factors' as MODY-responsible genes provided a breakthrough in the field of diabetes. Patients with HNF-1α and HNF-1β mutations, as well as their model mice, show impaired pancreatic β-cell function. The mechanism of impaired β-cell function and the target genes has been intensively investigated by considerable in vitro and in vivo studies. The insulin gene is one of the target genes of HNF-1α and HNF-1β in the β-cells, and may contribute to the diabetes. The IGF-1 gene is also regulated by HNF-1α and HNF-1β, and its decreased expression may contribute to growth failure and impaired β-cell proliferation. Mutations in HNF-1β result in symptoms in multiple organs, including kidney and liver, and several target genes have been reported to be involved in the pathogenesis. HNF-1α and HNF-1β may be one of the master regulators of hepatocyte and islet transcription, and further investigations by microarray and genome-scale analyses are providing information for the better understanding of the complex transcriptional network involving HNF-1α and -1β.

Keywords: diabetes mellitus; hepatocyte nuclear factor-1α; hepatocyte nuclear factor-1β; insulin; IGF-1; maturity-onset diabetes of the young; transcription factor

Document Type: Research article

DOI: http://dx.doi.org/10.1586/17446651.3.4.441

Affiliations: 1: Department of Pediatrics, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan., Email: sachi-tky@umin.ac.jp

Publication date: 2008-07-01

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• Expert Review of Endocrinology & Metabolism provides extensive coverage of state-of-the-art research and clinical advancements in the field of endocrine control and metabolism, with a focus on screening, prevention, diagnostics, existing and novel therapeutics, as well as related molecular genetics, pathophysiology and epidemiology
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