title: The effects of exercise training and caloric restriction on the cardiac oxytocin natriuretic peptide system in the diabetic mouse.
abstract: BACKGROUND
  Regular exercise training (ET) and caloric restriction (CR) are the frontline strategies in the treatment of type 2 diabetes mellitus with the aim at reducing cardiometabolic risk. ET and CR improve body weight and glycemic control, and experimental studies indicate that these paradigms afford cardioprotection. In this study, the effects of combined ET and CR on the cardioprotective oxytocin (OT)-natriuretic peptide (NP) system were determined in the db/db mouse, a model of type 2 diabetes associated with insulin resistance, hyperglycemia, and obesity.
  
  
  METHODS
  Five-week-old male db/db mice were assigned to the following groups: sedentary, ET, and ET + CR. Nonobese heterozygote littermates served as controls. ET was performed on a treadmill at moderate intensity, and CR was induced by reducing food intake by 30% of that consumed by sedentary db/db mice for a period of 8 weeks.
  
  
  RESULTS
  After 8 weeks, only ET + CR, but not ET, slightly improved body weight compared to sedentary db/db mice. Regardless of the treatment, db/db mice remained hyperglycemic. Hearts from db/db mice demonstrated reduced expression of genes linked to the cardiac OT-NP system. In fact, compared to control mice, mRNA expression of GATA binding protein 4 (GATA4), OT receptor, OT, brain NP, NP receptor type C, and endothelial nitric oxide synthase (eNOS) was decreased in hearts from sedentary db/db mice. Both ET alone and ET + CR increased the mRNA expression of GATA4 compared to sedentary db/db mice. Only ET combined with CR produced increased eNOS mRNA and protein expression.
  
  
  CONCLUSIONS
  Our data indicate that enhancement of eNOS by combined ET and CR may improve coronary endothelial vasodilator dysfunction in type 2 diabetes but did not prevent the downregulation of cardiac expression in the OT-NP system, possibly resulting from the sustained hyperglycemia and obesity in diabetic mice.
authors.affiliation: Department of Physiology, Laboratory of Diabetes and Exercise Metabolism, Midwestern University, Glendale, AZ, USA.
authors.forename: Tom L
authors.initials: TL
authors.lastname: Broderick
authors.affiliation: Department of Medicine, Laboratory of Cardiovascular Biochemistry, Centre Hospitalier de l'Université de Montréal-Hôtel-Dieu, Montréal, QC, Canada.
authors.forename: Marek
authors.initials: M
authors.lastname: Jankowski
authors.affiliation: Department of Medicine, Laboratory of Cardiovascular Biochemistry, Centre Hospitalier de l'Université de Montréal-Hôtel-Dieu, Montréal, QC, Canada.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Gutkowska
keywords: GATA4; db/db; diabetes; natriuretic peptides; oxytocin; running