| Reversal of preexisting hyperglycemia in diabetic mice by acute deletion of the Men1 gene. | |
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MedLine Citation:
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PMID: 21059956 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A hallmark of diabetes is an absolute or relative reduction in the number of functional β cells. Therapies that could increase the number of endogenous β cells under diabetic conditions would be desirable. Prevalent gene targeting mouse models for assessing β-cell proliferation and diabetes pathogenesis only address whether deletion of a gene prevents the development of diabetes. Models testing whether acute excision of a single gene can ameliorate or reverse preexisting hyperglycemia in established diabetes remain to be explored, which could directly validate the effect of gene excision on treating diabetes. Here, we report that acute and temporally controlled excision of the Men1 gene, which encodes menin, ameliorated preexisting hyperglycemia in streptozotocin-treated mice. Moreover, Men1 excision also improved the preexisting hyperglycemia and glucose intolerance in genetic db/db diabetic mice. Furthermore, acute Men1 excision reversed preexisting glucose intolerance in high-fat diet-fed mice. Men1 excision improved glucose metabolism at least partly through increasing proliferation of endogenous β cells and islet size. Acute Men1 excision up-regulated a group of proproliferative genes in pancreatic islets. Together, these findings demonstrate that established hyperglycemia can be reversed through repression of a single gene, Men1, in diabetic conditions, and suggest that menin is a vital regulator in pathogenesis of diabetes. |
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Authors:
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Yuqing Yang; Buddha Gurung; Ting Wu; Haoren Wang; Doris A Stoffers; Xianxin Hua |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-11-08 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 107 ISSN: 1091-6490 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-11-24 Completed Date: 2011-01-20 Revised Date: 2011-07-28 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 20358-63 Citation Subset: IM |
Affiliation:
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Abramson Family Cancer Research Institute, Department of Cancer Biology, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blotting, Western Cell Proliferation Diabetes Mellitus, Experimental* Enzyme-Linked Immunosorbent Assay Gene Deletion* Gene Expression Profiling Gene Expression Regulation / physiology* Glucose Tolerance Test Hyperglycemia / genetics* Immunohistochemistry Insulin / blood, secretion Insulin-Secreting Cells / cytology*, secretion Male Mice Mice, Transgenic Oligonucleotide Array Sequence Analysis Proto-Oncogene Proteins / genetics* Reverse Transcriptase Polymerase Chain Reaction |
| Grant Support | |
ID/Acronym/Agency:
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R01 DK068157/DK/NIDDK NIH HHS; R01-CA-113962/CA/NCI NIH HHS; R01-DK085121/DK/NIDDK NIH HHS; R56-DK08512/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Men1 protein, mouse; 0/Proto-Oncogene Proteins; 11061-68-0/Insulin |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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