Glucose-dependent insulinotropic polypeptide and tissue inflammation: Implications for atherogenic cardiovascular disease

Glucose-dependent insulinotropic polypeptide (GIP) has pleiotropic actions on pancreatic endocrine function, adipose tissue lipid metabolism, and skeletal calcium metabolism. Recent data indicate a potential new role for GIP in the pathogenesis of cardiovascular disease. This review focuses on the emerging literature that highlights GIP’s role in inflammation—an established process in the initiation and progression of atherosclerosis. In vasculature tissue, GIP may reduce concentrations of circulating inflammatory cytokines, attenuate vascular endothelial inflammation, and directly limit atherosclerotic vascular damage. Important to recognize is that evidence exists to support both pro- and anti-inflammatory effects of GIP even within the same tissue/cell type. Therefore, future study designs must account for factors such as model heterogeneity, physiological relevance of doses/exposures, potential indirect effects on inflammatory pathways, and the glucose-dependent insulinotropic polypeptide receptor (GIPR) agonist form. Elucidating the specific effects of enhanced GIP signaling in vascular inflammation and atherosclerosis is crucial given the existing widespread use of DPP4 inhibitors and the emergence of dual-incretin receptor agonists for type 2 diabetes treatment.