Menin controls growth of pancreatic beta-cells in pregnant mice and promotes gestational diabetes mellitus

Science. 2007 Nov 2;318(5851):806-9. doi: 10.1126/science.1146812.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Diabetes, Gestational / etiology*
  • Diabetes, Gestational / metabolism
  • Female
  • Humans
  • Insulin / metabolism
  • Insulin-Secreting Cells / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Obesity / metabolism
  • Pregnancy
  • Prolactin / metabolism
  • Proto-Oncogene Proteins / physiology*
  • Tumor Cells, Cultured

Substances

  • Insulin
  • MEN1 protein, human
  • Men1 protein, mouse
  • Proto-Oncogene Proteins
  • Prolactin