Document Detail

Glucose-Mediated Repression of Menin Promotes Pancreatic β-Cell Proliferation.
MedLine Citation:
PMID:  22166975     Owner:  NLM     Status:  Publisher    
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.
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
Related Documents :
20477555 - Alendronate-loaded microparticles for improvement of intestinal cellular absorption.
7289925 - Hyaluronidase, from wound healing to cancer.
18436625 - Identification and characterization of rabbit small intestinal villus cell brush border...
11993845 - The effects of intravenously administered methylxanthine preparations on the glycoconju...
18553815 - Regeneration of nad(p)h by immobilized whole cells of clostridium butyricum under hydro...
20654565 - In vitro assessment of paracetamol-induced toxicity in the rat reuber hepatoma h4iiec3/...
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:  -    
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.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Allopregnanolone Prevents Dieldrin-Induced NMDA Receptor Internalization and Neurotoxicity by Preser...
Next Document:  Rapid estrogen receptor-mediated mechanisms determine the sexually dimorphic sensitivity of ventricu...