한빛사논문
- 조회281
Hye‑Yoon Jeon†, Chan‑Hee Moon†, Eun‑Bin Kim, Nilofar Danishmalik Sayyed, Ah‑Jun Lee and Kwon‑Soo Ha*
Department of Molecular and Cellular Biochemistry, Kangwon National University School of Medicine, Chuncheon 24341, Kangwon‑Do, Korea
†Hye-Yoon Jeon and Chan-Hee Moon contributed equally to this work.
*Correspondence: Kwon‑Soo Ha
Abstract
Background: Hyperglycemic memory (HGM) is a pivotal phenomenon in the development of diabetic complications. Although coincident diabetic complications are reported, research on their development and treatment is limited. Thus, we investigated whether C-peptide can simultaneously inhibit HGM-induced retinal, pulmonary, and glomerular dysfunctions in diabetic mice supplemented with insulin.
Methods: Insulin-treated diabetic mice were supplemented with human C-peptide by subcutaneous implantation of K9-C-peptide depots for 4 weeks, and reactive oxygen species (ROS) generation, transglutaminase (TGase) activity, and vascular leakage were examined in the retina, lung, and kidney.
Results: We found hyperglycemia-induced persistent ROS generation and TGase activation after blood glucose normalization in the retina, lung, and kidney of insulin-supplemented diabetic mice. These pathological events were inhibited by systemic supplementation of human C-peptide via subcutaneous implantation of a thermosensitive biopolymer-conjugated C-peptide depot. ROS generation and TGase activation were in a vicious cycle after glucose normalization, and C-peptide suppressed the vicious cycle and subsequent endothelial permeability in human retinal endothelial cells. Moreover, C-peptide supplementation ameliorated HGM-induced retinal vascular leakage and neurodegeneration, pulmonary vascular leakage and fibrosis, and glomerular adherens junction disruption and vascular leakage.
Conclusions: Overall, our findings demonstrate that C-peptide supplementation simultaneously attenuates vascular and neuronal dysfunctions in the retina, lung, and glomerulus of insulin-supplemented diabetic mice.
논문정보
- Research article
- 2023년 02월 (BRIC 등록일 2023-04-14)
- 국내 연구진
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