Exercise and IGF‐1 supplementation improve angiogenesis and angiogenic cytokines in a rat model of diabetes‐induced neuropathy

NEW FINDINGS: What is the central question of this study? Do changes in the level of angiogenesis related mediators (VEGF-A, TSP-1 and NF-Kappab) in sciatic nerve mediate diabetic neuropathy in the Streptozotocin-induced type 1 diabetic male rat? Can exercise and IGF-I treatment improve diabetes related-decreased angiogenesis in the sciatic nerve of Streptozotocin-induced type 1 diabetic male rat? What is the main finding and it's important? VEGF-A, TSP-1 and NF-Kappab levels change in the sciatic nerve of diabetic rats and may mediate diabetic neuropathy. Treatment with IGF-I and exercise could increase angiogenesis in the diabetic rats by increasing VEGF-A as well as decreasing TSP-1 and NF-Kappab expression in the sciatic nerve.However, combination therapy didn't show any additive effect on angiogenesis or VEGF-A, TSP-1 and NF-Kappab levels in the sciatic nerve of the diabetic rats compared with eachtreatmrnt alone. ABSTRACT: Background Diabetic neuropathy is a severe complication of diabetes , affecting 40-50% of diabetic people in the world. This study aimed to characterize angiogenesis alterations and related molecular mediators in the sciatic nerve under diabetic conditions alone or in combination with exercise and insulin-like growth factor 1 (IGF-1) administration. Methods Forty male Wistar rats were assigned into one of five groups, namely control, diabetes, diabetes+exercise, diabetes+IGF-1, and diabetes+exercise+IGF-1. Type 1 diabetes was induced by intraperitoneal injection of 60 mg kg(-1) of streptozotocin. After 30 days of treatment with exercise or IGF-I alone or in combination, diabetic neuropathy was evaluated by a hot plate, HbA1c was measured, angiogenesis was determined by immunostaining for PECAM-1/CD31, and expressions of vascular endothelial growth factor-A (VEGF-A), thrombospondin-1 (TSP-1) and nuclear factor kappa B (NF-Kb) were determined by ELISA. Results After four weeks, the diabetes group showed a significant decrease in capillary density and VEGF-A levels, but a significant increase in HbA1c in blood, TSP-1 and NF-Kb levels in the sciatic nerve compared to the control group, whereas these effects were reversed by exercise and IGF-1. However, simultaneous treatment of diabetic rats with IGF-I and exercise did not have any synergistic effects. Conclusions These findings indicate that diabetes-induced neuropathy may in part be associated with decreased angiogenesis mediated by overproduction of TSP-1 and NF-Kb, as well as reduced production of VEGF-A proteins. The findings also showed that exercise and IGF-I can reduce neuropathy followed by increased angiogenesis by change of TSP-1, NF-Kb and VEGF-A production levels. This article is protected by copyright. All rights reserved.