title: Deletion of the Men1 gene prevents streptozotocin-induced hyperglycemia in mice.
abstract: Diabetes ultimately results from an inadequate number of functional beta cells in the islets of Langerhans. Enhancing proliferation of functional endogenous beta cells to treat diabetes remains underexplored. Here, we report that excision of the Men1 gene, whose loss-of-function mutation leads to inherited multiple endocrine neoplasia type 1 (MEN1), rendered resistant to streptozotocin-induced hyperglycemia in a tamoxifen-inducible and temporally controlled Men1 excision mouse model as well as in a tissue-specific Men1 excision mouse model. Men1 excision prevented mice from streptozotocin-induced hyperglycemia mainly through increasing the number of functional beta cells. BrdU incorporation by beta cells, islet size, and circulating insulin levels were significantly increased in Men1-excised mice. Membrane localization of glucose transporter 2 was largely preserved in Men1-excised beta cells, but not in Men1-expressing beta cells. Our findings suggest that repression of menin, a protein encoded by the Men1 gene, might be a valuable means to maintain or increase the number of functional endogenous beta cells to prevent or ameliorate diabetes.
authors.affiliation: Abramson Family Cancer Research Institute, Department of Cancer Biology, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Yang
authors.forename: Haoren
authors.initials: H
authors.lastname: Wang
authors.forename: Xianxin
authors.initials: X
authors.lastname: Hua
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D003921:Diabetes Mellitus, Experimental / Q000517:prevention & control*; D051273:Glucose Transporter Type 2 / Q000032:analysis; D006943:Hyperglycemia / Q000517:prevention & control*; D050417:Insulin-Secreting Cells / Q000502:physiology; D008297:Male; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D013311:Streptozocin
chemical_list: D051273:Glucose Transporter Type 2; C484898:Men1 protein, mouse; D011518:Proto-Oncogene Proteins; C495682:Slc2a2 protein, mouse; D013311:Streptozocin