Gestational Diabetes Mellitus Resulting From Impaired β-Cell Compensation in the Absence of FoxM1, a Novel Downstream Effector of Placental Lactogen

• DOI: 10.2337/db09-0050
• Publication Date: 2009-10-16T01:25:15Z
• Authors: Hongjie Zhang; Jia Zhang; Christine F. Pope; Laura A. Crawford; Rupangi C. Vasavada; Shubhada M. Jagasia; Maureen Gannon
• Keywords: Neogenesis; Placental lactogen; Human placental lactogen; FOXM1

OBJECTIVE The objectives of the study were to determine whether cell cycle transcription factor, FoxM1, is required for glucose homeostasis and β-cell mass expansion in maternal islets during pregnancy FoxM1 essential placental lactogen (PL)-induced proliferation. RESEARCH DESIGN AND METHODS β-Cell mass, proliferation, assessed virgin, pregnant, postpartum mice with a pancreas-wide Foxm1 deletion (FoxM1Δpanc). Wild-type cultured or without PL examined induction. Transgenic overexpressing β-cells bred FoxM1Δpanc mice, proliferation was examined. RESULTS upregulated pregnancy. In contrast controls, did not increase pregnant females. Mutant showed increased Menin nuclear p27. females developed gestational diabetes mellitus as progressed. After parturition, euglycemia restored females, but islet size significantly reduced. Strikingly, normal pancreata due combination neogenesis. Evidence neogenesis included number endocrine clusters, proportion smaller islets, neurogenin 3 insulin expression cells adjacent ducts. induced PL-mediated increases vivo. CONCLUSIONS compensation absence pancreata. Our results suggest that functions downstream mediate its effects on