Swimming training promotes angiogenesis of endothelial progenitor cells by upregulating IGF1 expression and activating the PI3K/AKT pathway in type 2 diabetic rats

Abstract

The present study aimed to investigate the effect of swimming training on the angiogenesis of endothelial progenitor cells (EPCs) in type 2 diabetes mellitus (T2DM) rats by upregulating the insulin-like growth factor 1 (IGF1) expression and to reveal its potential mechanism of action. Male Sprague-Dawley rats were divided into the Control, Model, Model train, Model train + short interfering (si)-NC and Model train + si-IGF1 groups. Serum glucose levels were measured using the oral glucose tolerance test. EPCs were isolated from the bone marrow cavity and identified through morphological observation and immunofluorescence staining. The expression of IGF-1 mRNA in rat serum and EPCs was analyzed by reverse transcription-quantitative PCR. The fasting insulin levels in serum were assessed by ELISA. Cell Counting Kit-8, scratch assay and tube formation assay were used to determine the cell viability, migration and tube formation of rat EPCs, and western blotting was employed to measure the expression levels of IGF1, phosphoinositide 3-kinase (PI3K), phosphorylated-PI3K, protein kinase B (AKT) and phosphorylated-AKT. The present study demonstrated that swimming training significantly decreased the glucose levels and homeostatic model assessment of insulin resistance scores, but increased the fasting insulin levels and IGF1 mRNA expression. Microscopic observation and immunofluorescence identification suggested that EPCs were successfully isolated. In addition, swimming training markedly elevated the levels of IGF1 and promoted cell viability, migration and tube formation in rat EPCs. Furthermore, IGF1 knockdown experiments indicated that swimming training might play a regulatory role by elevating the IGF1 expression to activate the PI3K/AKT pathway. Overall, swimming training promoted the angiogenesis of EPCs in T2DM rats and its potential mechanism may be related to the upregulation of IGF1 expression and the activation of the PI3K/AKT pathway.