title: Menin controls growth of pancreatic beta-cells in pregnant mice and promotes gestational diabetes mellitus.
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 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.
authors.affiliation: Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Satyajit K
authors.initials: SK
authors.lastname: Karnik
authors.forename: Hainan
authors.initials: H
authors.lastname: Chen
authors.forename: Graeme W
authors.initials: GW
authors.lastname: McLean
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Heit
authors.forename: Xueying
authors.initials: X
authors.lastname: Gu
authors.forename: Andrew Y
authors.initials: AY
authors.lastname: Zhang
authors.forename: Magali
authors.initials: M
authors.lastname: Fontaine
authors.forename: Michael H
authors.initials: MH
authors.lastname: Yen
authors.forename: Seung K
authors.initials: SK
authors.lastname: Kim
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D016640:Diabetes, Gestational / Q000209:etiology* / Q000378:metabolism; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009765:Obesity / Q000378:metabolism; D011247:Pregnancy; D011388:Prolactin / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D014407:Tumor Cells, Cultured
chemical_list: D007328:Insulin; C105373:MEN1 protein, human; C484898:Men1 protein, mouse; D011518:Proto-Oncogene Proteins; D011388:Prolactin