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This Article Full Text Full Text (PDF) All Versions of this Article: JME-08-0080v1 41/4/229    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Au, W.-S. Articles by Lin, M. C Search for Related Content PubMed PubMed Citation Articles by Au, W.-S. Articles by Lin, M. C

Department of Chemistry, Institute of Molecular Technology for Drug Discovery and Synthesis, The University of Hong Kong, Room 8N-11, Kadoorie Biological Science Building, Pokfulam Road, Hong Kong, China¹ Department of Pathology, The University of Hong Kong, Hong Kong, China² Institute of Molecular and Chemical Biology, East China Normal University, Shanghai 200062, China³ Centre of Emerging Infectious Diseases, The Chinese University of Hong Kong, Hong Kong, China

(Correspondence should be addressed to M C Lin Email: mcllin{at}hkusua.hku.hk)

Insulin inhibits the transcription of the microsomal triglyceride transfer protein (MTTP), which plays a pivotal role in lipoprotein assembly and secretion. Here, we provide evidence that a hepatocyte nuclear factor 1 binding element (HNF1A element) within the MTTP promoter serves as a novel negative insulin-responsive element. Deletion/mutation mapping of the MTTP gene promoter identified a modified HNF1A element that is crucial to the negative insulin effect. Chimeric promoter containing this HNF1A element and minimal TEAD1 promoter also responded negatively toward insulin treatment. Gel shift assay demonstrated that HNF1A but not HNF1B binds to this element. Enforced expression of HNF1A was sufficient to reconstitute the negative insulin responsiveness of MTTP promoter in TM4SF1 myocytes that are HNF1A negative. Furthermore, replacing this element with consensus HNF1A element preserved the negative insulin response, suggesting that negative insulin responsiveness is a generic characteristic of HNF1A element. Given that many genes implicated in diabetes contain HNF1A element, the potential regulation of these genes by insulin via HNF1A element may provide important clues for the manifestation and treatment of diabetic metabolic syndromes.