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Glucose-Mediated Repression of Menin Promotes Pancreatic β-Cell Proliferation.
MedLine Citation:
PMID:  22166975     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  JOURNAL ARTICLE     Date:  2011-12-13
Journal Detail:
Title:  Endocrinology     Volume:  -     ISSN:  1945-7170     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
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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