Loss of HGF/c-Met Signaling in Pancreatic β-Cells Leads to Incomplete Maternal β-Cell Adaptation and Gestational Diabetes Mellitus

• DOI: 10.2337/db11-1154
• Publication Date: 2012-03-17T01:46:45Z
• Authors: Cem Demirci; Sara Ernst; Juan C. Alvarez-P...; Taylor Rosa; Shelley Valle; Varsha Shridhar; Gabriella P. Casi...; Laura C. Alonso; Rupangi C. Vasavada; Adolfo García-Ocana
• Keywords: GLUT2

Hepatocyte growth factor (HGF) is a mitogen and insulinotropic agent for the β-cell. However, whether HGF/c-Met has role in maternal β-cell adaptation during pregnancy unknown. To address this issue, we characterized glucose homeostasis pregnant mice lacking c-Met pancreas (PancMet KO mice). Circulating HGF islet expression were increased mice. Importantly, PancMet displayed decreased replication apoptosis at gestational day (GD)15. The was associated with reductions prolactin receptor levels, STAT5 nuclear localization forkhead box M1 mRNA, upregulation of p27. Furthermore, mouse β-cells more sensitive to dexamethasone-induced cytotoxicity, whereas protected human against dexamethasone vitro. These detrimental alterations proliferation death led incomplete mass expansion GD19 early postpartum periods. accompanied by blood glucose, plasma insulin, impaired tolerance. islets failed upregulate GLUT2 pancreatic duodenal homeobox-1 insulin content, glucose-stimulated secretion gestation. studies indicate that signaling essential its absence/attenuation leads diabetes mellitus.