Anti-inflammatory and angiogenic effects of exercise training in cardiac muscle of diabetic mice

Tom L Broderick; Jacqueline M Sennott; Jolanta Gutkowska; Marek Jankowski

doi:10.2147/DMSO.S197127

Anti-inflammatory and angiogenic effects of exercise training in cardiac muscle of diabetic mice

Diabetes Metab Syndr Obes. 2019 Apr 26:12:565-573. doi: 10.2147/DMSO.S197127. eCollection 2019.

Authors

Tom L Broderick¹, Jacqueline M Sennott², Jolanta Gutkowska³, Marek Jankowski³

Affiliations

¹ Laboratory of Diabetes and Exercise Metabolism, Department of Physiology, College of Graduate Studies, Midwestern University, Glendale, AZ, USA.
² Department of Cardiology, Medical Education H23, Saint-Joseph Mercy Health System, Pontiac, MI, USA.
³ Cardiovascular Biochemistry Laboratory, CRCHUM (7-134), Department of Medicine, University of Montreal, Montreal, Quebec, Canada.

Abstract

Background: Improved glycemic control and cardiovascular function are major benefits of regular exercise training (ET) in type 2 diabetes. Recent work has demonstrated that ET improves cardiac and vascular functions independent of obesity, inflammation, and glucose control in the diabetic db/db mouse. In this study, we determined whether ET can overcome the effects of elevated inflammatory cytokines and hyperglycemia on markers of cardiac angiogenesis and inflammation in the diabetic mouse. Methods: Male diabetic db/db mice were assigned to a sedentary and exercise-trained group. Sedentary lean control littermates were used as controls. ET was performed at moderate intensity on a treadmill 5 days a week for a period of 8 weeks. After ET, blood was collected for assay of glucose, hemoglobin (HB and HB_1AC), C-reactive protein (CRP), and IL-6. Markers of inflammation and insulin resistance (IL-6, IL-1β, and tumor necrosis factor-alpha [TNF-α]) and angiogenesis (endothelial nitric oxide synthase [eNOS], vascular endothelial growth factor-A [VEGF-A], and hypoxia-inducible factor-1α [HIF-1α]) were measured in hearts. Results: Diabetic db/db mice remained obese and hyperglycemic after ET. Percent total HB and HB_1AC were significantly higher in ET db/db mice compared to sedentary db/db mice, indicating further deterioration of glucose control with ET. Plasma levels of CRP and IL-6 were higher in sedentary db/db mice compared to control mice and were unaffected by ET. However, in the presence of hyperglycemia and elevated plasma cytokines, protein expression of eNOS, mRNA expression of VEGF-A, and HIF-1α was increased in db/db hearts after ET. On the other hand, protein expression of TNF-α and mRNA expression IL-6 and IL-1β was significantly decreased by ET in hearts of db/db mice. Conclusion: Our results indicate that ET improves cardiac markers of angiogenesis, insulin resistance, and endothelial dysfunction in the db/db mouse. This was observed independently of obesity, hyperglycemia, and the systemic inflammatory state.

Keywords: angiogenesis; db/db; exercise; glycated hemoglobin; inflammation.