IGFBP-2 Ameliorates Vascular Insulin Resistance and Contributes to Cardiometabolism

Abstract

Insulin-like growth factor binding protein-2 (IGFBP-2) has been implicated in the etiology of insulin resistance. And previous studies have pointed that IGFBP-2 overexpression could prevent age-related hypertension. The present study was aimed to document the modulation of dual vascular actions of IGFBP-2 in human umbilical vein endothelial cells (HUVECs). HUVECs at passage 4-6 were cultured with either 20 μM hydrogen peroxide (H2O2) or 2mM glucosamine (GLU) to induce insulin resistance, which declined the expression of IGFBP-2 in HUVECs and resulted in endothelial nitric oxide (NO) and endothelin-1 (ET-1) production were reduced significantly compare to those control cells (p<0.01), the suppression of NO production was more notable. The insulin-induced phosphorylation of Akt at The3and endothelial NO synthase (eNOS) at Ser1177 were also slightly decreased in IGFBP-2 down-regulated HUVECS. Coherently, insulin-induced phosphorylated eNOS and extracellular signal-related kinase 1/2 (ERK1/2) were 3.5 (p<0.01) and 1.5 (p<0.05) folds increased by an overnight IGFBP-2 treatment, respectively. As the production of ET-1 was mediated by ERK1/2 and the secretion of NO was regulated by eNOS, we suspected that IGFBP-2 played an important role on endothelial diastolic and systolic function, may robustly improved vasodilation more than vasoconstriction in insulin resistant HUVECs. Disclosure Z. Li: None. Y. Lv: None. W. Guo: None. G. Wang: None.