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Glucose-mediated repression of menin promotes pancreatic beta-cell proliferation.

Authors: Zhang, H  Li, W  Wang, Q  Wang, X  Li, F  Zhang, C  Wu, L  Long, H  Liu, Y  Li, X  Luo, M  Li, G  Ning, G 
Citation: Zhang H, etal., Endocrinology. 2012 Feb;153(2):602-11. doi: 10.1210/en.2011-1460. Epub 2011 Dec 13.
Pubmed: (View Article at PubMed) PMID:22166975
DOI: Full-text: DOI:10.1210/en.2011-1460

Menin, encoded by the Men1 gene, is responsible for beta-cell tumor formation in patients with multiple endocrine neoplasia type 1. Recently, menin has been proven to negatively regulate beta-cell proliferation during pregnancy. However, it is unclear whether menin is involved in pancreatic beta-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 beta-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 beta-cells.

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CRRD Object Information
CRRD ID: 9589127
Created: 2014-11-10
Species: All species
Last Modified: 2014-11-10
Status: ACTIVE



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