Characterization of Multiple Signaling Pathways of Insulin in the Regulation of Vascular Endothelial Growth Factor Expression in Vascular Cells and Angiogenesis

Abstract

The effects of insulin on vascular endothelial growth factor (VEGF) expression in cultured vascular cells and in angiogenesis were characterized. Insulin increased VEGF mRNA levels in mouse aortic smooth muscle cells from 10 ؊9 to 10 ؊7 M with an initial peak of 3.7-fold increases at 1 h and a second peak of 2.8-fold after 12 h.

High glucose attenuates insulin-induced VEGF expression in bovine retinal microvascular endothelial cells

“…11 Some found that insulin-induced VEGF expression was through both PI3-K and P42/44 MAPK pathways in HepG2 cells and in mouse aortic smooth muscle cells. 22,23 In this study, we found insulin upregulated VEGF in BRECs through PI3-K signalling pathways.…”

Insulin activates hypoxia-inducible factor-1α in human and rat vascular smooth muscle cells via phosphatidylinositol-3 kinase and mitogen-activated protein kinase pathways: impairment in insulin resistance owing to defects in insulin signalling

“…In addition, this study shows that in VSMC insulin activates signalling pathways that are involved in vasomotion, cell growth and migration, among them the PI3-K/Akt and MAPK pathways [3,4,24]. The involvement of both the PI3-K and MAPK pathways in the insulin-induced modulation of HIF-1α synthesis is not surprising because the same pathways influence the increase of this transcription factor by IGF-1 in colon carcinoma cells [25], and are responsible for the insulin-induced activation of VEGF mRNA [3] and protein [4] expression in VSMC.…”

“…The involvement of both the PI3-K and MAPK pathways in the insulin-induced modulation of HIF-1α synthesis is not surprising because the same pathways influence the increase of this transcription factor by IGF-1 in colon carcinoma cells [25], and are responsible for the insulin-induced activation of VEGF mRNA [3] and protein [4] expression in VSMC. The MAPK pathway consists of three main parallel cascades: ERK, JNK and p38 MAPK [26].…”

“…In vascular smooth muscle cells (VSMC) insulin increases VEGF mRNA expression [3] and protein synthesis [4] via both phosphatidylinositol 3-kinase (PI3-K) and mitogen-activated protein kinase (MAPK) pathways [3,4]. This insulin effect is blunted in obese, insulin-resistant Zucker fa/fa rats [4], which represent an animal model of insulin resistance [5].…”

MicroRNA-126 inhibits cell viability and invasion in a diabetic retinopathy model via targeting IRS-1

“…A previous study reported that activation of PI3K/Akt signaling pathway upregulates the expression of VEGF through a direct interaction with the VEGF promoter (7). Regulation ofPI3K/Akt activation is essential for the long term upregulation of VEGF (8). These previous studies suggested that the IRS-1/PI3K/Akt/VEGF pathway may be a promising molecular target for the prevention and treatment of DR.…”