摘要：SummaryEndogenous humoral factors that link systemic and/or local insulin demand to pancreatic β-cells have not been identified. Here, we demonstrated that T-cadherin, a unique glycosylphosphatidylinositol-anchored cadherin primarily expressed in vascular endothelial cells and cardiac and skeletal muscle cells, but not in pancreatic β-cells, was secreted as soluble forms and was important for β-cell proliferation.Cdh13(T-cadherin) knockout mice exhibited impaired glucose handling due to attenuated β-cell proliferation under high-fat diet conditions. The gene expression analyses indicated the impairment in cell cycle and Notch signaling in the islets of T-cadherin knockout mice under high-fat diet conditions. In streptozotocin-induced diabetes, the replacement of soluble T-cadherin improved β-cell mass and blood glucose levels in T-cadherin knockout mice. Recombinant soluble T-cadherin upregulated Notch signaling in cultured murine islets. We concluded that soluble T-cadherin could work as an endogenous humoral factor whose signaling pathways including Notch signaling regulate β-cell proliferation under diabetic conditions in mice.Graphical abstractDisplay OmittedHighlights•Loss of T-cadherin impairs glucose tolerance and reduces β-cell mass in DIO•Soluble T-cadherin improves glucose metabolism and β-cell mass in STZ diabetes•Soluble T-cadherin promotes β-cell proliferation in DIO•Soluble T-cadherin upregulates Notch signaling and cell cycle in isolated isletsMolecular biology; Immunology; Cell biology.
