[PMID]: | 28356733 |
[Au] Autor: | Zhao SJ; Wang DH; Li YW; Han L; Xiao X; Ma M; Wan DC; Hong A; Ma Y |
[Ad] Endereço: | Institute of Biomedicine, Department of Cellular Biology, Jinan University; National Engineering Research Center of Genetic Medicine, Key Laboratory of Bioengineering Medicine of Guangdong Province, Jinan University. |
[Ti] Título: | A novel selective VPAC2 agonist peptide-conjugated chitosan modified selenium nanoparticles with enhanced anti-type 2 diabetes synergy effects. |
[So] Source: | Int J Nanomedicine;12:2143-2160, 2017. |
[Is] ISSN: | 1178-2013 |
[Cp] País de publicação: | New Zealand |
[La] Idioma: | eng |
[Ab] Resumo: | A novel neuroendocrine peptide, pituitary adenylate cyclase activating peptide (PACAP), was found to have an important role in carbohydrate or lipid metabolism and was susceptible to dipeptidyl peptidase IV degradation. It can not only mediate glucose-dependent insulin secretion and lower blood glucose by activating VPAC2 receptor, but also raise blood glucose by promoting glucagon production by VPAC1 receptor activation. Therefore, its therapeutic application is restricted by the exceedingly short-acting half-life and the stimulatory function for glycogenolysis. Herein, we generated novel peptide-conjugated selenium nanoparticles (SeNPs; named as SCD), comprising a 32-amino acid PACAP-derived peptide DBAYL that selectively binds to VPAC2, and chitosan-modified SeNPs (SeNPs-CTS, SC) as slow-release carrier. The circulating half-life of SCD is 14.12 h in mice, which is 168.4-and 7.1-fold longer than wild PACAP (~5 min) and DBAYL (~1.98 h), respectively. SCD (10 nmol/L) significantly promotes INS-1 cell proliferation, glucose uptake, insulin secretion, insulin receptor expression and also obviously reduces intracellular reactive oxygen species levels in H O -injured INS-1 cells. Furthermore, the biological effects of SCD are stronger than Exendin-4 (a clinically approved drug through its insulinotropic effect), DBAYL, SeNPs or SC. A single injection of SCD (20 nmol/kg) into db/db mice with type 2 diabetes leads to enhanced insulin secretion and sustained hypoglycemic effect, and the effectiveness and duration of SCD in enhancing insulin secretion and reducing blood glucose levels are much stronger than Exendin-4, SeNPs or SC. In db/db mice, chronic administration of SCD by daily injection for 12 weeks markedly improved glucose and lipid profiles, insulin sensitivity and the structures of pancreatic and adipose tissue. The results indicate that SC can play a role as a carrier for the slow release of bioactive peptides and SCD could be a hopeful therapeutic against type 2 diabetes through the synergy effects of DBAYL and SeNPs. |
[Mh] Termos MeSH primário: |
Quitosana/química Diabetes Mellitus Tipo 2/tratamento farmacológico Nanopartículas/química Peptídeos/uso terapêutico Receptores Tipo II de Peptídeo Intestinal Vasoativo/agonistas Selênio/química
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[Mh] Termos MeSH secundário: |
Animais Glicemia/metabolismo Proliferação Celular/efeitos dos fármacos Diabetes Mellitus Tipo 2/patologia Liberação Controlada de Fármacos Jejum/sangue Glucose/metabolismo Glucose/farmacologia Meia-Vida Peróxido de Hidrogênio/toxicidade Insulina/genética Insulina/metabolismo Resistência à Insulina Masculino Camundongos Peptídeos/farmacologia RNA Mensageiro/genética RNA Mensageiro/metabolismo Espécies Reativas de Oxigênio/metabolismo Receptor de Insulina/metabolismo Peçonhas/uso terapêutico
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Blood Glucose); 0 (Insulin); 0 (Peptides); 0 (RNA, Messenger); 0 (Reactive Oxygen Species); 0 (Receptors, Vasoactive Intestinal Peptide, Type II); 0 (Venoms); 9012-76-4 (Chitosan); 9P1872D4OL (exenatide); BBX060AN9V (Hydrogen Peroxide); EC 2.7.10.1 (Receptor, Insulin); H6241UJ22B (Selenium); IY9XDZ35W2 (Glucose) |
[Em] Mês de entrada: | 1705 |
[Cu] Atualização por classe: | 170522 |
[Lr] Data última revisão:
| 170522 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 170331 |
[St] Status: | MEDLINE |
[do] DOI: | 10.2147/IJN.S130566 |
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