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Exercise and insulin-like growth factor 1 supplementation improve angiogenesis and angiogenic cytokines in a rat model of diabetes-induced neuropathy.

Abstract：

NEW FINDINGS:What is the central question of this study? Do changes in levels of angiogenesis-related mediators [vascular endothelial growth factor-A (VEGF-A), thrombospondin-1 (TSP-1) and nuclear factor-κB (NF-κB)] in the sciatic nerve mediate diabetic neuropathy in the streptozotocin-induced type 1 diabetic male rat? Can exercise and insulin-like growth factor 1 (IGF-I) treatment improve the diabetes-related decrease in angiogenesis in sciatic nerve in these animals? What is the main finding and its importance? Levels of VEGF-A, TSP-1 and NF-κB change in the sciatic nerve of diabetic rats and might mediate diabetic neuropathy. Treatment with IGF-I and exercise could increase angiogenesis in the diabetic rats by increasing VEGF-A and decreasing TSP-1 and NF-κB expression in the sciatic nerve. ABSTRACT:Diabetic neuropathy is a severe complication of diabetes that affects 40-50% of diabetic people in the world. The aim of this study was to characterize alterations in angiogenesis and related molecular mediators in the sciatic nerve in diabetic conditions alone or in diabetes in combination with exercise and/or administration of insulin-like growth factor 1 (IGF-I). Forty male Wistar rats were assigned into one of five groups, namely control, diabetes, diabetes + exercise, diabetes + IGF-I and diabetes + exercise + IGF-I. Type 1 diabetes was induced by i.p. injection of streptozotocin (60 mg kg-1 ). After 30 days of treatment with exercise or IGF-I alone or in combination, diabetic neuropathy was evaluated with a hotplate, glycated haemoglobin 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-κB (NF-κB) were determined by enzyme-linked immunosorbent assay.After 4 weeks, the diabetes group showed a significant decrease in capillary density and VEGF-A levels, but a significant increase in glycated haemoglobin in blood, TSP-1 and NF-κB levels in the sciatic nerve compared with the control group, and these effects were ameliorated by exercise and IGF-I. However, simultaneous treatment of diabetic rats with IGF-I and exercise did not have any synergistic effects. These findings indicate that diabetes-induced neuropathy may be associated, in part, with decreased angiogenesis mediated by overproduction of TSP-1 and NF-κB, in addition to reduced production of VEGF-A. The findings also showed that exercise and IGF-I can reduce neuropathy, followed by increased angiogenesis, by changes in TSP-1, NF-κB and VEGF-A production levels.

journal_name

Exp Physiol

journal_title

Experimental physiology

authors

Saboory E,Gholizadeh-Ghaleh Aziz S,Samadi M,Biabanghard A,Chodari L

doi

10.1113/EP088069

subject

Has Abstract

pub_date

2020-05-01 00:00:00

pages

783-792

issue

eissn

0958-0670

issn

1469-445X

journal_volume

105

pub_type

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Exercise and insulin-like growth factor 1 supplementation improve angiogenesis and angiogenic cytokines in a rat model of diabetes-induced neuropathy.