Document Detail

Menin controls growth of pancreatic beta-cells in pregnant mice and promotes gestational diabetes mellitus.
MedLine Citation:
PMID:  17975067     Owner:  NLM     Status:  MEDLINE    
During pregnancy, maternal pancreatic islets grow to match dynamic physiological demands, but the mechanisms regulating adaptive islet growth in this setting are poorly understood. Here we show that menin, a protein previously characterized as an endocrine tumor suppressor and transcriptional regulator, controls islet growth in pregnant mice. Pregnancy stimulated proliferation of maternal pancreatic islet beta-cells that was accompanied by reduced islet levels of menin and its targets. Transgenic expression of menin in maternal beta-cells prevented islet expansion and led to hyperglycemia and impaired glucose tolerance, hallmark features of gestational diabetes. Prolactin, a hormonal regulator of pregnancy, repressed islet menin levels and stimulated beta-cell proliferation. These results expand our understanding of mechanisms underlying diabetes pathogenesis and reveal potential targets for therapy in diabetes.
Satyajit K Karnik; Hainan Chen; Graeme W McLean; Jeremy J Heit; Xueying Gu; Andrew Y Zhang; Magali Fontaine; Michael H Yen; Seung K Kim
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Science (New York, N.Y.)     Volume:  318     ISSN:  1095-9203     ISO Abbreviation:  Science     Publication Date:  2007 Nov 
Date Detail:
Created Date:  2007-11-02     Completed Date:  2007-11-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0404511     Medline TA:  Science     Country:  United States    
Other Details:
Languages:  eng     Pagination:  806-9     Citation Subset:  IM    
Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA.
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MeSH Terms
Cell Proliferation
Diabetes, Gestational / etiology*,  metabolism
Insulin / metabolism
Insulin-Secreting Cells / physiology*
Mice, Inbred C57BL
Mice, Transgenic
Obesity / metabolism
Prolactin / metabolism
Proto-Oncogene Proteins / physiology*
Tumor Cells, Cultured
Grant Support
Reg. No./Substance:
0/MEN1 protein, human; 0/Men1 protein, mouse; 0/Proto-Oncogene Proteins; 11061-68-0/Insulin; 9002-62-4/Prolactin
Comment In:
Science. 2007 Nov 2;318(5851):729   [PMID:  17975038 ]

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