Glucagon-like Peptide 1 Can Directly Protect the Heart Against Ischemia/Reperfusion Injury

Bose AK, Mocanu MM, Carr RD, Brand CL, Yellon DM. Diabetes. 2005;54:146-151.

Glucagon-like peptide-1 (GLP-1) is an incretin hormone that stimulates meal-response insulin release and is currently being studied as a potential treatment for type 2 diabetes. Although the antidiabetic properties of GLP-1 have been established in previous studies, this is the first study to show that GLP-1 also has cardioprotective effects against myocardial infarction in an animal model.

The effect of GLP-1 on infarction was assessed using rat myocardium in the presence (in vivo) and absence (in vitro) of endogenous insulin. In the in vivo model, GLP-1 plus valine pyrrolidide (VP; a dipeptidyl peptidase IV [DPP-IV] inhibitor) added prior to ischemia showed a significant decrease in infarction compared with the VP-only and control groups (20.0±2.8% vs 47.3±4.3% vs 44.3±2.4%, respectively; P<.001; n=8 per group). Similar results were obtained using the in vitro model (GLP-1 + VP: 26.7±2.7%, VP: 52.6±4.7%, control: 58.7±4.1%; P<.0001).

Antagonists and inhibitors of GLP-1 activity were used to determine the potential mechanistic basis of the cardioprotective effect of GLP-1, and results suggest GLP-1 is involved in a number of pathways acting in parallel to confer a cardioprotective effect. Exendin (9-39) (a GLP-1 receptor antagonist), Rp-Camp (a cAMP inhibitor), LY294002 (a PI3kinase inhibitor), and UO126 (a p42/44 mitogen-activated protein kinase inhibitor) were all shown to abolish the protective effect of GLP-1 against myocardial infarction in vitro.

In summary, these findings suggest GLP-1 may have dual benefits in the treatment of type 2 diabetes as both an anti-diabetic and cardioprotective agent.