西亚试剂：Menin Controls Growth of Pancreatic ß-Cells in Pregnant Mic

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

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.

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