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Peer-reviewedCC BY 4.0Bioscience Reports

IGFBP2 attenuates high glucose-induced endothelial dysfunction through PI3K/Akt/eNOS pathway activation

  • Xiaoyu Song1
  • Wentao Zhong1
  • Chengqian Chen2
  • Hao Zheng1
  • Zhuo Li1
  1. 1Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, China
  2. 2Department of Hematology, The First Hospital of Jilin University, Changchun, China
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Abstract

Endothelial dysfunction induced by hyperglycemia is a key event in diabetic vascular complications and is closely associated with impaired PI3K/Akt/endothelial nitric oxide synthase (eNOS) signaling. Insulin-like growth factor-binding protein 2 (IGFBP2) has been implicated in metabolic regulation and cell survival, but its role in high glucose (HG)-induced endothelial injury remains unclear. In the present study, human umbilical vein endothelial cells (HUVECs) were exposed to HG (33 mM) for 24 h and then treated with recombinant human IGFBP2 (rhIGFBP2, 200 ng/ml) for 60 min. HG reduced Akt/eNOS phosphorylation and nitric oxide (NO) production, increased the expression of ICAM-1, VCAM-1, and SELE, promoted interleukin-6, interleukin-8, monocyte chemoattractant protein-1 secretion, and enhanced apoptosis. rhIGFBP2 attenuated these HG-induced changes by restoring PI3K/Akt/eNOS signaling and NO production, reducing inflammatory activation, and decreasing apoptotic cell percentage. The effect of rhIGFBP2 on Akt/eNOS phosphorylation and NO production was broadly comparable to that of insulin under HG conditions. HG also increased p38 MAPK phosphorylation, whereas rhIGFBP2 showed only a nonsignificant decreasing trend. Importantly, PI3K inhibition with LY294002 abolished rhIGFBP2-induced Akt/eNOS activation, supporting the involvement of the PI3K/Akt/eNOS pathway. These findings suggest that IGFBP2 protects against HG-induced endothelial dysfunction mainly by activating PI3K/Akt/eNOS signaling and may represent a potential mediator of endothelial protection under diabetic conditions.

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Cite

BibTeXRIS
BibTeX
@article{song2026igfbp2,
  title = {{IGFBP2 attenuates high glucose-induced endothelial dysfunction through PI3K/Akt/eNOS pathway activation}},
  author = {Xiaoyu Song and Wentao Zhong and Chengqian Chen and Hao Zheng and Zhuo Li},
  journal = {Bioscience Reports},
  year = {2026},
  month = oct,
  doi = {10.1042/bsr20260182},
  url = {https://doi.org/10.1042/bsr20260182},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - IGFBP2 attenuates high glucose-induced endothelial dysfunction through PI3K/Akt/eNOS pathway activation
AU  - Xiaoyu Song
AU  - Wentao Zhong
AU  - Chengqian Chen
AU  - Hao Zheng
AU  - Zhuo Li
PY  - 2026
DA  - 2026/10/29
JO  - Bioscience Reports
DO  - 10.1042/bsr20260182
UR  - https://doi.org/10.1042/bsr20260182
AB  - Endothelial dysfunction induced by hyperglycemia is a key event in diabetic vascular complications and is closely associated with impaired PI3K/Akt/endothelial nitric oxide synthase (eNOS) signaling. Insulin-like growth factor-binding protein 2 (IGFBP2) has been implicated in metabolic regulation and cell survival, but its role in high glucose (HG)-induced endothelial injury remains unclear. In the present study, human umbilical vein endothelial cells (HUVECs) were exposed to HG (33 mM) for 24 h and then treated with recombinant human IGFBP2 (rhIGFBP2, 200 ng/ml) for 60 min. HG reduced Akt/eNOS phosphorylation and nitric oxide (NO) production, increased the expression of ICAM-1, VCAM-1, and SELE, promoted interleukin-6, interleukin-8, monocyte chemoattractant protein-1 secretion, and enhanced apoptosis. rhIGFBP2 attenuated these HG-induced changes by restoring PI3K/Akt/eNOS signaling and NO production, reducing inflammatory activation, and decreasing apoptotic cell percentage. The effect of rhIGFBP2 on Akt/eNOS phosphorylation and NO production was broadly comparable to that of insulin under HG conditions. HG also increased p38 MAPK phosphorylation, whereas rhIGFBP2 showed only a nonsignificant decreasing trend. Importantly, PI3K inhibition with LY294002 abolished rhIGFBP2-induced Akt/eNOS activation, supporting the involvement of the PI3K/Akt/eNOS pathway. These findings suggest that IGFBP2 protects against HG-induced endothelial dysfunction mainly by activating PI3K/Akt/eNOS signaling and may represent a potential mediator of endothelial protection under diabetic conditions.
SN  - 0144-8463
SN  - 1573-4935
ER  -