Glucose-Dependent Insulinotropic Polypeptide Suppresses Peripheral Arterial Remodeling in Male Mice
Abstract
Glucose-dependent insulinotropic polypeptide (GIP) exhibits direct cardiovascular actions in addition to its well-known insulinotropic effect. However, the role of GIP in peripheral artery disease remains unclear. In this study, we evaluated the effects of GIP against peripheral arterial remodeling in mouse models. The genetic deletion of GIP receptor (GIPR) led to exaggerated neointimal hyperplasia after transluminal femoral artery wire injury. Conversely, chronic GIP infusion suppressed neointimal hyperplasia and facilitated endothelial regeneration. The beneficial effects of GIP were abrogated by inhibiting nitric oxide (NO) synthase, suggesting a possible mechanism mediated by NO. In cultured human umbilical vein endothelial cells (HUVECs), GIP elevated cytosolic calcium levels without affecting intracellular cAMP levels. Furthermore, GIP dose-dependently increased NO production, whereas this effect was abolished by inhibiting AMP-activated protein kinase (AMPK). GIP induced AMPK phosphorylation, which was abrogated by inhibiting phospholipase C and calcium-calmodulin-dependent protein kinase kinase but not by adenylate cyclase or liver kinase B1, suggesting the existence of a calcium-mediated GIPR signaling pathway. These ...Continue Reading
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GIP as a Potential Therapeutic Target for Atherosclerotic Cardiovascular Disease-A Systematic Review
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