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A novel glucose-responsive element in the human insulin gene functions uniquely in primary cultured islets

Item Type:Article
Title:A novel glucose-responsive element in the human insulin gene functions uniquely in primary cultured islets
Creators Name:Sander, M. and Griffen, S.C. and Huang, J. and German, M.S.
Abstract:Insulin gene transcription is limited to the beta cells within the mammalian pancreas and, like insulin secretion, is regulated by glucose. Our previous studies in primary cultured beta cells suggested the presence of a strong glucose-responsive enhancer element between base pairs -341 and -260 of the human insulin promoter, the same region in which a transcriptional repressor had been identified in beta-cell tumor lines. In an attempt to map these promoter activities and resolve these conflicting data, we designed minienhancer constructs spanning this region, and tested them in primary cultured and immortalized cells. One sequence, the Z element (base pairs -292 to -243), functions as both a potent glucose-responsive transcriptional enhancer in primary cultured islet cells and as a transcriptional repressor in immortalized beta and nonbeta cells and in primary fibroblasts. In addition, the Z element binds a novel glucose-responsive protein complex that is found in the nuclei of primary cultured islet cells, but not in the nuclei of tumor cells or primary cultured fibroblasts. These data demonstrate a critical role for the Z element in human insulin gene transcription and its regulation by glucose.
Keywords:Base Sequence, Binding Sites, Cultured Cells, DNA, Genetic Enhancer Elements, Glucose, Insulin, Islets of Langerhans, Site-Directed Mutagenesis, Genetic Promoter Regions, Sprague-Dawley Rats, Transfection, Animals, Mice, Rats
Source:Proceedings of the National Academy of Sciences of the United States of America
Publisher:National Academy of Sciences
Page Range:11572-7
Date:29 September 1998
Official Publication:https://doi.org/10.1073/pnas.95.20.11572
PubMed:View item in PubMed

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