Soluble T-cadherin secretion from endothelial cells is regulated via insulin/PI3K/Akt signalling

Mice, Knockout Male Endothelial cells Insulin demand Insulin signalling 610 Endothelial Cells Cadherins Receptor, Insulin Mice Phosphatidylinositol 3-Kinases soluble T-cadherin Human Umbilical Vein Endothelial Cells Animals Humans Insulin Receptors, Leptin Female Peptides Proto-Oncogene Proteins c-akt Signal Transduction
DOI: 10.1016/j.bbrc.2024.150403 Publication Date: 2024-07-14T10:44:26Z
ABSTRACT
Our recent report showed that soluble T-cadherin promotes pancreatic beta-cell proliferation. However, how and where the secretion of soluble T-cadherin is regulated remain unclear.Soluble T-cadherin levels significantly increased in leptin receptor-deficient db/db mice with hypoinsulinaemia or in wild-type mice treated with insulin receptor blockade by S961. Similar results were observed in human subjects; Diabetic ketoacidosis patients at the time of hospitalization had increased plasma soluble T-cadherin levels, which decreased after insulin infusion therapy. Patients with recurrent ovarian cancer who were administered a phosphatidylinositol-3 kinase (PI3K)-alpha inhibitor (a new anticancer drug) had increased plasma soluble T-cadherin and plasma C-peptide levels. Endothelial cell-specific T-cadherin knockout mice, but not skeletal muscle- or cardiac muscle-specific T-cadherin knockout mice, showed a 26 % reduction in plasma soluble T-cadherin levels and a significant increase in blood glucose levels in streptozocin-induced diabetes. The secretion of soluble T-cadherin from human endothelial cells was approximately 20 % decreased by insulin and this decrease was canceled by blockade of insulin receptor/Akt signalling, not Erk signalling.We conclude that insulin regulates soluble T-cadherin levels and soluble T-cadherin secretion from endothelial cells is positively regulated by insulin/insulin receptor/Akt signalling.
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