Oxytocin and cardioprotection in diabetes and obesity.
Oxytocin (OT) emerges as a drug for the treatment of diabetes and obesity. The entire OT system is synthesized in the rat and human heart. The direct myocardial infusion with OT into an ischemic or failing heart has the potential to elicit a variety of cardioprotective effects. OT treatment attenuates cardiomyocyte (CMs) death induced by ischemia-reperfusion by activating pro-survival pathways within injured CMs in vivo and in isolated cells. OT treatment reduces cardiac apoptosis, fibrosis, and hypertrophy. The OT/OT receptor (OTR) system is downregulated in the db/db mouse model of type 2 diabetes which develops genetic diabetic cardiomyopathy (DC) similar to human disease. We have shown that chronic OT treatment prevents the development of DC in the db/db mouse. In addition, OT stimulates glucose uptake in both cardiac stem cells and CMs, and increases cell resistance to diabetic conditions. OT may help replace lost CMs by stimulating the in situ differentiation of cardiac stem cells into functional mature CMs. Lastly, adult stem cells amenable for transplantation such as MSCs could be preconditioned with OT ex vivo and implanted into the injured heart to aid in tissue regeneration through direct differentiation, secretion of protective and cardiomyogenic factors and/or their fusion with injured CMs.
Cardiovascular Biochemistry Laboratory, CRCHUM (7-134), Tour Viger, 900 St-Denis St., Montreal, Quebec, H2X 0A9, Canada. marek.jankowski@umontreal.ca.|Department of Medicine, Faculty of Medicine, University of Montreal, Montreal, Canada. marek.jankowski@umontreal.ca.
Marek
M
Jankowski
Department of Physiology, Laboratory of Diabetes and Exercise Metabolism, Midwestern University, Agave Hall, office 217-B, 19555 North 59th Avenue, Glendale, AZ, 85308, USA. tbrode@midwestern.edu.
Tom L
TL
Broderick
Cardiovascular Biochemistry Laboratory, CRCHUM (7-134), Tour Viger, 900 St-Denis St., Montreal, Quebec, H2X 0A9, Canada.|Department of Medicine, Faculty of Medicine, University of Montreal, Montreal, Canada.
Jolanta
J
Gutkowska
D000818:Animals; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D003920:Diabetes Mellitus / Q000188:drug therapy*; D015444:Exercise; D006801:Humans; D051379:Mice; D008962:Models, Theoretical; D009206:Myocardium / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy*; D018384:Oxidative Stress; D010121:Oxytocin / Q000378:metabolism / Q000627:therapeutic use*; D051381:Rats; D015398:Signal Transduction
D002316:Cardiotonic Agents; D010121:Oxytocin
Cardiomyocyte; Cardioprotection; Differentiation; Heart; Oxytocin; Stem cells