Shani Puyesky, Mohammed Egbaria, Dunia Ali Naser, Anat Schonblum, Lena Kabha, Iael Fuhrman, Limor Landsman
Despite extensive research on the role of the hepatocyte growth factor (HGF)/c-Met pathway in β-cells and glucose homeostasis, the endogenous source of HGF in islets remains unclear. This study characterizes the pancreatic source of HGF and its physiological requirement in vivo. Pericytes were identified as the primary endogenous source of HGF in human and mouse islets. Pericytic HGF loss causes glucose intolerance by impairing insulin production through the regulation of key β-cell genes. Establishing β-cell mass during embryogenesis and pregnancy depends on mesenchymal/pericytic HGF. This study establishes the islet vasculature as a source of trophic factors required for glycemic control.