Glucagon-Like Peptide-1 Protects Against Cardiac Microvascular Injury in Diabetes via a cAMP/PKA/Rho- Dependent Mechanism

Impaired cardiac microvascular function contributes to cardio-vascular complications in diabetes. Glucagon-like peptide-1 (GLP-1) exhibits potential cardioprotective properties in addition to its glucose-lowering effect. This study was designed to evaluate the impact of GLP-1 on cardiac microvascular injury in diabetes and the underlying mechanism involved. Experimental diabetes was induced using streptozotocin in rats. Cohorts of diabetic rats received a 12-week treatment of vildagliptin (dipep-tidyl peptidase-4 inhibitor) or exenatide (GLP-1 analog). Exper-imental diabetes attenuated cardiac function, glucose uptake, and microvascular barrier function, which were significantly improved by vildagliptin or exenatide treatment. Cardiac micro-vascular endothelial cells (CMECs) were isolated and cultured in normal or high glucose medium with or without GLP-1. GLP-1 decreased high-glucose–induced reactive oxygen species pro