IGF-I combined with exercise improve diabetes-induced vascular dysfunction in heart of male Wistar rats

Abstract

Introduction: This research investigates the impact of insulin-like growth factor-I (IGF -I)and exercise on mediators associated with angiogenesis (VEGF-A, TSP-1, and NF-кβ) and capillarization status of the diabetic rats’ hearts. Methods: Splitting of forty Wistar male rats into five groups occurred as following: control,diabetes, diabetes+IGF-I, diabetes+exercise, and diabetes+exercise+IGF-I.Through intraperitoneal administration of 60 mg/kg streptozotocin, the condition of Type 1diabetes was escalated. After four weeks of treatment with IGF-I (2 mg/kg/day) or treadmill exercise (17 m/min, zero degrees slope, 30 min/day), in the heart, microvascular density and protein levels of VEGF-A, TSP-1, and NF-кβ were determined by H & E staining and ELISA,respectively. Results: Within the diabetic group, observations present a significant decrease in VEGF-A and MVD levels, whereas an increase in the TSP-1 and NF-Κb levels. While these impacts were reversed by either IGF-I or exercise treatments, simultaneous treatment had synergistic effects. Moreover, among diabetic rats, undesirable histologic alterations of the heart were demonstrated, including myonecrosis, interstitial edema, hemorrhage, and mononuclear immune cell infiltration, whereas treatments improved these changes. Conclusion: These data manifest that IGF-I and exercise can increase the cardiac angiogenesis of diabetic rats through increasing expression of VEGF-A, and decreasing TSP-1 and NF-кβproteins level, also can improve myocardial tissue damages.