Effect of thymosin beta 4 in the presence of up-regulation of the insulin-like growth factor-1 signaling pathway on high-glucose-exposed vascular endothelial cells

Thymosin beta 4 (Tβ₄), which regulates vascular cell growth, can ameliorate some of the problems associated with diabetes. However, the precise signaling mechanisms by which Tβ₄ protects against hyperglycemia-induced damage to endothelial cells have not been investigated in detail. Thus, the aim of this study was to elucidate the role of Tβ₄ in diabetes and the possible involvement of insulin-like growth factor-1 (IGF-1), which affects cellular survival, metabolism, and glucose homeostasis in high-glucose (HG)-injured human umbilical vein endothelial cells (HUVECs). Immunoblotting assays revealed that under HG blockade conditions, Tβ₄ did not alter the insulin-signaling pathway, but induced overexpression of IGF-1 protein, leading to activation of factors in alternative signaling pathway. Small interfering RNA of Tβ₄ and IGF-1 were studied to clarify relationship between Tβ4 and IGF-1. These findings suggest that IGF-1 induction by Tβ₄ ameliorates the damage in HG-injured HUVECs which manifest as diabetic vascular disorder.