Continuous stimulation of dual-function peptide PGLP-1-VP inhibits the morbidity and mortality of NOD mice through anti-inflammation and immunoregulation

Abstract Multiple animal and human studies have shown that administration of GLP-1RA can enhance β-cell recovery, reduce insulin dosage, reduce HbA1c content in the blood, reduce the risk of hypoglycemia and reduce inflammation. In the NOD mouse model, peptide VP treatment can prevent and treat type...

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Autores principales: Huashan Gao, Qian Zhao, Shanshan Tang, Kaiying Li, Fujian Qin, Ziwei Song, Yi Pan, Liang Jin, Yanfeng Zhang
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:e447863a899842fc87907b30a959e33f2021-12-02T14:11:32ZContinuous stimulation of dual-function peptide PGLP-1-VP inhibits the morbidity and mortality of NOD mice through anti-inflammation and immunoregulation10.1038/s41598-021-83201-42045-2322https://doaj.org/article/e447863a899842fc87907b30a959e33f2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83201-4https://doaj.org/toc/2045-2322Abstract Multiple animal and human studies have shown that administration of GLP-1RA can enhance β-cell recovery, reduce insulin dosage, reduce HbA1c content in the blood, reduce the risk of hypoglycemia and reduce inflammation. In the NOD mouse model, peptide VP treatment can prevent and treat type 1 diabetes through immunomodulation. Therefore, we designed a new dual-functional PGLP-1-VP, which is expected to combine the anti-inflammatory effect of PGLP-1 and the immunomodulatory effect of VP peptide. In streptozotocin-induced hyperglycemic mice model, we demonstrated that PGLP-1-VP can act as a GLP-1R agonist to improve hyperglycemia and increase insulin sensitivity. In the NOD mouse model, PGLP-1-VP treatment reduced morbidity, mortality, and pancreatic inflammation, and showed superior effect to PGLP-1 or VP treatment alone, confirming that PGLP-1-VP may act as a dual-function peptide. PGLP-1-VP provided immunomodulatory effect through increasing Th2 cell percentage and balancing the ratio of Th2/Th1 in spleen and PLN, similar to P277 and VP. Additionally, PGLP-1-VP and PGLP-1 act the anti-inflammation by increasing Treg cells and TGF-β1 content like DPP-IV inhibitor. Taken together, our data shows that the dual-functional PGLP-1-VP reduces morbidity and mortality in the NOD model, suggesting a potential role in preventing and treating type 1 diabetes.Huashan GaoQian ZhaoShanshan TangKaiying LiFujian QinZiwei SongYi PanLiang JinYanfeng ZhangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Huashan Gao
Qian Zhao
Shanshan Tang
Kaiying Li
Fujian Qin
Ziwei Song
Yi Pan
Liang Jin
Yanfeng Zhang
Continuous stimulation of dual-function peptide PGLP-1-VP inhibits the morbidity and mortality of NOD mice through anti-inflammation and immunoregulation
description Abstract Multiple animal and human studies have shown that administration of GLP-1RA can enhance β-cell recovery, reduce insulin dosage, reduce HbA1c content in the blood, reduce the risk of hypoglycemia and reduce inflammation. In the NOD mouse model, peptide VP treatment can prevent and treat type 1 diabetes through immunomodulation. Therefore, we designed a new dual-functional PGLP-1-VP, which is expected to combine the anti-inflammatory effect of PGLP-1 and the immunomodulatory effect of VP peptide. In streptozotocin-induced hyperglycemic mice model, we demonstrated that PGLP-1-VP can act as a GLP-1R agonist to improve hyperglycemia and increase insulin sensitivity. In the NOD mouse model, PGLP-1-VP treatment reduced morbidity, mortality, and pancreatic inflammation, and showed superior effect to PGLP-1 or VP treatment alone, confirming that PGLP-1-VP may act as a dual-function peptide. PGLP-1-VP provided immunomodulatory effect through increasing Th2 cell percentage and balancing the ratio of Th2/Th1 in spleen and PLN, similar to P277 and VP. Additionally, PGLP-1-VP and PGLP-1 act the anti-inflammation by increasing Treg cells and TGF-β1 content like DPP-IV inhibitor. Taken together, our data shows that the dual-functional PGLP-1-VP reduces morbidity and mortality in the NOD model, suggesting a potential role in preventing and treating type 1 diabetes.
format article
author Huashan Gao
Qian Zhao
Shanshan Tang
Kaiying Li
Fujian Qin
Ziwei Song
Yi Pan
Liang Jin
Yanfeng Zhang
author_facet Huashan Gao
Qian Zhao
Shanshan Tang
Kaiying Li
Fujian Qin
Ziwei Song
Yi Pan
Liang Jin
Yanfeng Zhang
author_sort Huashan Gao
title Continuous stimulation of dual-function peptide PGLP-1-VP inhibits the morbidity and mortality of NOD mice through anti-inflammation and immunoregulation
title_short Continuous stimulation of dual-function peptide PGLP-1-VP inhibits the morbidity and mortality of NOD mice through anti-inflammation and immunoregulation
title_full Continuous stimulation of dual-function peptide PGLP-1-VP inhibits the morbidity and mortality of NOD mice through anti-inflammation and immunoregulation
title_fullStr Continuous stimulation of dual-function peptide PGLP-1-VP inhibits the morbidity and mortality of NOD mice through anti-inflammation and immunoregulation
title_full_unstemmed Continuous stimulation of dual-function peptide PGLP-1-VP inhibits the morbidity and mortality of NOD mice through anti-inflammation and immunoregulation
title_sort continuous stimulation of dual-function peptide pglp-1-vp inhibits the morbidity and mortality of nod mice through anti-inflammation and immunoregulation
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/e447863a899842fc87907b30a959e33f
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