T-cadherin attenuates insulin-dependent signalling, eNOS activation, and angiogenesis in vascular endothelial cells

Abstract

T-cad expression modulates signalling and functional responses of EC to insulin. We have identified a novel signalling mechanism regulating insulin function in the endothelium and attribute a role for T-cad up-regulation in the pathogenesis of endothelial InsRes.

Fibroblast Growth Factor 21 Protects Against High Glucose Induced Cellular Damage and Dysfunction of Endothelial Nitric-Oxide Synthase in Endothelial Cells

“…Ser-633 of eNOS is phosphorylated by Akt [57], cAMP-dependent protein kinase A (PKA) [60] and AMPK [61]. The phosphorylation of eNOS also plays important roles in other pathophysiological process such as myocardial infarction and vascular insulin sensitivity [62,63,64]. To explore how FGF21 regulates these two sites phosphorylation, we used chemical inhibitors to selectively block these signaling pathways.…”

T-cadherin Is Essential for Adiponectin-mediated Revascularization*

“…However, it has been reported that T-cadherin can function independently of adiponectin by promoting LDL-induced intracellular calcium release (57), facilitating release of insulin from pancreatic ␤-cells (58) and inhibiting insulin signaling in endothelial cells via the PI3K/Akt/mammalian target of rapamycin axis (33). Because T-cadherin is found to co-localize with caveolin, it is possible that interactions between T-cadherin and other proteins in caveolae or lipid rafts may result in intracellular signaling (59).…”

“…T-cadherin is highly expressed in the vasculature including endothelial cells (24), smooth muscle cells (25), and pericytes (26). It has been implicated in modulation of angiogenic activities in cultured endothelial cells; however, some studies report that it promotes angiogenesis (27)(28)(29)(30)(31), whereas others report its attenuation (32,33). Importantly, T-cadherin has been shown to localize adiponectin to tumor vasculature (31) and heart tissue (47).…”

Apelinergic system in endothelial cells and its role in angiogenesis in myocardial ischemia

“…A link between AMPK and apelin was reported also for energy metabolism in adipose tissue [84] and myocardium [85] while involving additional proteins, such as insulin receptor substrate-1 (IRS-1) [85]. IRS-1 suggests itself potentially to be involved in the apelin-AMPK pathway in ECs, as it had been described to be expressed in ECs [86] and has an ability to mediate angiogenic effects [87].…”