| Glucose-stimulated translation regulation of insulin by the 5' UTR-binding proteins. | |
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MedLine Citation:
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PMID: 21357685 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Insulin is the key regulator of glucose homeostasis in mammals, and glucose-stimulated insulin biosynthesis is essential for maintaining glucose levels in a narrow range in mammals. Glucose specifically promotes the translation of insulin in pancreatic β-islet, and the untranslated regions of insulin mRNA play a role in such regulation. Specific factors in the β-islets bind to the insulin 5' UTR and regulate its translation. In the present study we identify protein-disulfide isomerase (PDI) as a key regulator of glucose-stimulated insulin biosynthesis. We show that both in vitro and in vivo PDI can specifically associate with the 5' UTR of insulin mRNA. Immunodepletion of PDI from the islet extract results in loss of glucose-stimulated translation indicating a critical role for PDI in insulin biosynthesis. Similarly, transient overexpression of PDI resulted in specific translation activation by glucose. We show that the RNA binding activity of PDI is mediated through PABP. PDI catalyzes the reduction of the PABP disulfide bond resulting in specific binding of PABP to the insulin 5' UTR. We also show that glucose stimulation of the islets results in activation of a specific kinase that can phosphorylate PDI. These findings identify PDI and PABP as important players in glucose homeostasis. |
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Authors:
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Shardul D Kulkarni; Bhavana Muralidharan; Amaresh C Panda; Baskar Bakthavachalu; Arya Vindu; Vasudevan Seshadri |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-02-28 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 286 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-04-18 Completed Date: 2011-06-28 Revised Date: 2012-04-23 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 14146-56 Citation Subset: IM |
Affiliation:
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National Centre for Cell Science, Ganeshkhind, Pune 411007, India. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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5' Untranslated Regions* Amino Acid Sequence Animals Catalysis Gene Expression Regulation* Glucose / metabolism* Insulin / metabolism Insulin-Secreting Cells / cytology* Mice Molecular Sequence Data Protein Biosynthesis Protein Disulfide-Isomerases / chemistry* Rats Rats, Wistar Sequence Homology, Amino Acid |
| Chemical | |
Reg. No./Substance:
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0/5' Untranslated Regions; 0/Insulin; 50-99-7/Glucose; EC 5.3.4.1/Protein Disulfide-Isomerases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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