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Science 318 (5851): 806-809

Copyright © 2007 by the American Association for the Advancement of Science

Menin Controls Growth of Pancreatic ß-Cells in Pregnant Mice and Promotes Gestational Diabetes Mellitus

Satyajit K. Karnik,1 Hainan Chen,1* Graeme W. McLean,1* Jeremy J. Heit,1* Xueying Gu,1 Andrew Y. Zhang,1 Magali Fontaine,2 Michael H. Yen,1,3 Seung K. Kim1,3{dagger}

Abstract: 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 ß-cells that was accompanied by reduced islet levels of menin and its targets. Transgenic expression of menin in maternal ß-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 ß-cell proliferation. These results expand our understanding of mechanisms underlying diabetes pathogenesis and reveal potential targets for therapy in diabetes.

1 Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA.
2 Department of Pathology, Stanford University, Stanford, CA 94305, USA.
3 Department of Medicine (Oncology Division), Stanford University, Stanford, CA 94305, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: seungkim{at}stanford.edu

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