Understanding the Cardiovascular Effects of Incretin.
Cardiovascular disease (CVD), a leading cause of death in patients with diabetes mellitus, has several pathogenic mechanisms that are well established. However, the traditional hypoglycemic agents do not have proven positive effects on macrovascular disease. Novel therapeutic agents target the incretin pathway including the glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) agonists and the dipeptidyl peptidase-4 inhibitors. The glucose-regulatory actions of these agents function by increasing insulin secretion and suppressing glucagon. They also act to increase weight loss not only by inhibiting gastric emptying, but also by reducing appetite.
Although GLP-1 and GLP-1R agonists have demonstrated beneficial effects on myocardium and vascular endothelium including coronary and peripheral mouse vessels, they also have anti-inflammatory and anti-atherogenic actions. These agents also have positive effects on the lipid profile and blood pressure. Although these cardioprotective actions seem to be beyond the effects of glucose control and weight loss, they are mediated through GLP-1R- or GLP-1R-independent actions of cleaved GLP-1 (9-36). Larger randomized controlled trials are necessary to elucidate the clinical promise of these beneficial CVD effects.
Combined stimulation of glucagon-like peptide-1 receptor and inhibition of cannabinoid CB1 receptor act synergistically to reduce food intake and body weight in the rat.
Acute activation of central Glp1 receptors enhances hepatic insulin action and insulin secretion in high fat-fed, insulin resistant mice.
The Gut Hormones PYY(3-36) and GLP-1(7-36 amide) Reduce Food Intake and Modulate Brain Activity in Appetite Centers in Humans.