Cardiovascular effects of incretins in diabetes.
Recent years have seen an enormous increase in the number of therapeutic agents available for lowering blood glucose levels in people with type 2 diabetes. Among these agents, the incretin mimetics glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) agonists and dipeptidyl peptidase 4 (DPP4) inhibitors have received particular attention for the potential of these interventions to positively impact on cardiovascular outcomes. Although the results of large-scale cardiovascular outcome trials eagerly are anticipated, an increasing body of literature from preclinical and early phase clinical studies has indicated that both GLP-1R agonists and DPP4 inhibitors may exert glucose-independent cardiovascular effects. Despite its role in glucose homeostasis, the GLP-1R is surprisingly widely distributed throughout the body, including in the heart. GLP-1 may exert its effects through both receptor-dependent and receptor-independent mechanisms and through the actions of both the intact peptide and its metabolites. In addition, DPP4 inhibition not only augments the circulating levels of incretin hormones, but it also holds the capacity to augment the activity of other biologically important substrates, most notably the small protein stromal cell-derived factor 1 alpha. Whether these collective functions will act to reduce cardiovascular events in patients remains to be determined.
Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital and University of Toronto, Ontario, Canada.
Andrew
A
Advani
Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital and University of Toronto, Ontario, Canada.
Antoinette
A
Bugyei-Twum
Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital and University of Toronto, Ontario, Canada. Electronic address: connellyk@smh.ca.
Kim A
KA
Connelly
D002318:Cardiovascular Diseases / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000517:prevention & control*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000187:drug effects*; D000077270:Exenatide; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000819:agonists* / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D054795:Incretins / Q000378:metabolism*; D000069450:Liraglutide; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects*; D010455:Peptides / Q000627:therapeutic use; D016896:Treatment Outcome; D014688:Venoms / Q000627:therapeutic use
D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D054795:Incretins; D010455:Peptides; D014688:Venoms; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide
GLP-1 (glucagon-like peptide-1); cardiac function; dipeptidyl peptidase 4; facteur dérivé des cellules stromales de type 1; fonctionnement cardiaque; glucagon-like peptide 1; incretin; incrétine; stromal cell-derived factor 1