| Glucose-Mediated Repression of Menin Promotes Pancreatic β-Cell Proliferation. | |
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MedLine Citation:
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PMID: 22166975 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Menin, encoded by the Men1 gene, is responsible for β-cell tumor formation in patients with multiple endocrine neoplasia type 1. Recently, menin has been proven to negatively regulate β-cell proliferation during pregnancy. However, it is unclear whether menin is involved in pancreatic β-cell proliferation in response to other physiological replication stimuli, such as glucose. In this study, we found that the menin level was significantly reduced in high glucose-treated INS1 cells and primary rat islets, both with increased proliferation. A similar observation was found in islets isolated from rats subjected to 72-h continuous glucose infusion. The glucose-induced proliferation was inhibited by menin overexpression. Further molecular studies showed that glucose-induced menin suppression was blocked by PI3K/Akt pathway inhibitors. A major PI3K/Akt substrate, Foxo1, was shown to enhance menin transcription levels by binding the promoter region of the Men1 gene. Therefore, we conclude that glucose inhibits menin expression via the PI3K/Akt/Foxo1 pathway and hence promotes pancreatic β-cell proliferation. Our study suggests that menin might serve as an important intracellular target of glucose to mediate the mitogenic effect that glucose exerts in pancreatic β-cells. |
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Authors:
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Hongli Zhang; Wenyi Li; Qidi Wang; Xiao Wang; Fengying Li; Cuiping Zhangr; Ling Wu; Hongmei Long; Yun Liu; Xiaoying Li; Min Luo; Guo Li; Guang Ning |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-13 |
Journal Detail:
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Title: Endocrinology Volume: - ISSN: 1945-7170 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-14 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0375040 Medline TA: Endocrinology Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Department of Endocrinology, Ruijin Hospital, Shanghai Jiaotong University Medical School, 200025, Shanghai, P.R. China. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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