title: Downregulation of oxytocin and natriuretic peptides in diabetes: possible implications in cardiomyopathy.
abstract: Regular physical activity is beneficial in preventing the risk of cardiovascular complications of diabetes. Recent studies showed a cardioprotective role of oxytocin (OT) to induce natriuretic peptides (NPs) and nitric oxide (NO) release. It is not known if the diabetic state is associated with a reduced OT-NPs-NO system and if exercise training improves this system. To address this, we investigated the effects of treadmill running using the db/db mouse model of type 2 diabetes. Eight-week-old db/db mice were subjected to running 5 days per week for a period of 8 weeks. The lean db/+ littermates were used as controls. Sedentary db/db mice were obese and hyperglycaemic, and exercise training was not effective in reducing body weight and the hyperglycaemic state. Compared to control mice, db/db mice had lower heart weight and heart-to-body weight ratios. In these mice, this was associated with augmented cardiac apoptosis, cardiomyocyte enlargement and collagen deposits. In addition, db/db mice displayed significant downregulation in gene expression of OT (76%), OT receptors (65%), atrial NP (ANP; 43%), brain NP (BNP; 87%) and endothelial nitric oxide synthase (eNOS) (54%) in the heart (P < 0.05). Exercise training had no effect on expression of these genes which were stimulated in control mice. In response to exercise training, the significant increment of anti-apoptotic Bcl-2 gene expression was observed only in control mice (P < 0.05). In conclusion, downregulation of the OT-NPs-NO system occurs in the heart of the young db/db mouse. Exercise training was not effective in reversing the defect, suggesting impairment of this cardiac protective system in diabetes.
authors.affiliation: Laboratory of Cardiovascular Biochemistry, Research Centre, Centre Hospitalier de L'Université de Montréal-Hôtel-Dieu, Montréal, Québec, Canada. jolanta.gutkowska@umontreal.ca
authors.forename: Jolanta
authors.initials: J
authors.lastname: Gutkowska
authors.forename: Tom L
authors.initials: TL
authors.lastname: Broderick
authors.forename: Danalache
authors.initials: D
authors.lastname: Bogdan
authors.forename: Donghao
authors.initials: D
authors.lastname: Wang
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Lavoie
authors.forename: Marek
authors.initials: M
authors.lastname: Jankowski
mesh_terms: D000818:Animals; D001483:Base Sequence; D009202:Cardiomyopathies / Q000209:etiology* / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D017931:DNA Primers / Q000235:genetics; D048909:Diabetes Complications / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000235:genetics* / Q000628:therapy; D004195:Disease Models, Animal; D015536:Down-Regulation; D019254:Genes, bcl-2; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D045265:Natriuretic Peptides / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D010121:Oxytocin / Q000235:genetics*; D010805:Physical Conditioning, Animal; D005082:Physical Exertion; D018045:Receptors, Oxytocin / Q000235:genetics; D012307:Risk Factors
chemical_list: D017931:DNA Primers; D045265:Natriuretic Peptides; D018045:Receptors, Oxytocin; D010121:Oxytocin; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse
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