| First Author | Okita T | Year | 2022 |
| Journal | iScience | Volume | 25 |
| Issue | 11 | Pages | 105404 |
| PubMed ID | 36439986 | Mgi Jnum | J:350470 |
| Mgi Id | MGI:7397848 | Doi | 10.1016/j.isci.2022.105404 |
| Citation | Okita T, et al. (2022) Soluble T-cadherin promotes pancreatic beta-cell proliferation by upregulating Notch signaling. iScience 25(11):105404 |
| abstractText | Endogenous humoral factors that link systemic and/or local insulin demand to pancreatic beta-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 beta-cells, was secreted as soluble forms and was important for beta-cell proliferation. Cdh13 (T-cadherin) knockout mice exhibited impaired glucose handling due to attenuated beta-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 beta-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 beta-cell proliferation under diabetic conditions in mice. |
