A novel selective VPAC2 agonist peptide-conjugated chitosan modified selenium nanoparticles with enhanced anti-type 2 diabetes synergy effects

Shao-Jun Zhao,1,2,* De-Hua Wang,1,2 Yan-Wei Li,1,2 Lei Han,1,2 Xing Xiao,1,2 Min Ma,3,* David Chi-Cheong Wan,4 An Hong,1,2 Yi Ma1,2 1Institute of Biomedicine, Department of Cellular Biology, Jinan University, 2National Engineering Research Center of Genetic Medicine, Key Laboratory of Bioengineerin...

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Autores principales:	Zhao SJ, Wang DH, Li YW, Han L, Xiao X, Ma M, Wan DC, Hong A, Ma Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	pituitary adenylate cyclase activating peptide (PACAP)-derived peptide nano-selenium VPAC2 receptor synergy effect type 2 diabetes (T2D) Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/2c4da66d5a8f49aeb79eb0c9e773df2a
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spelling	oai:doaj.org-article:2c4da66d5a8f49aeb79eb0c9e773df2a2021-12-02T01:04:02ZA novel selective VPAC2 agonist peptide-conjugated chitosan modified selenium nanoparticles with enhanced anti-type 2 diabetes synergy effects1178-2013https://doaj.org/article/2c4da66d5a8f49aeb79eb0c9e773df2a2017-03-01T00:00:00Zhttps://www.dovepress.com/a-novel-selective-vpac2-agonist-peptide-conjugated-chitosan-modified-s-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Shao-Jun Zhao,1,2,* De-Hua Wang,1,2 Yan-Wei Li,1,2 Lei Han,1,2 Xing Xiao,1,2 Min Ma,3,* David Chi-Cheong Wan,4 An Hong,1,2 Yi Ma1,2 1Institute of Biomedicine, Department of Cellular Biology, Jinan University, 2National Engineering Research Center of Genetic Medicine, Key Laboratory of Bioengineering Medicine of Guangdong Province, Jinan University, 3College of traditional Chinese Medicine, Institute of Integrated Traditional Chinese and Western Medicine, Jinan University, Guangdong, 4School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, People’s Republic of China *These authors contributed equally to this work Abstract: 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 H2O2-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. Keywords: pituitary adenylate cyclase activating peptide (PACAP)-derived peptide, nano-selenium, VPAC2 receptor, synergy effect, type 2 diabetes (T2D)Zhao SJWang DHLi YWHan LXiao XMa MWan DCHong AMa YDove Medical Pressarticlepituitary adenylate cyclase activating peptide (PACAP)-derived peptidenano-seleniumVPAC2 receptorsynergy effecttype 2 diabetes (T2D)Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 2143-2160 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	pituitary adenylate cyclase activating peptide (PACAP)-derived peptide nano-selenium VPAC2 receptor synergy effect type 2 diabetes (T2D) Medicine (General) R5-920
spellingShingle	pituitary adenylate cyclase activating peptide (PACAP)-derived peptide nano-selenium VPAC2 receptor synergy effect type 2 diabetes (T2D) Medicine (General) R5-920 Zhao SJ Wang DH Li YW Han L Xiao X Ma M Wan DC Hong A Ma Y A novel selective VPAC2 agonist peptide-conjugated chitosan modified selenium nanoparticles with enhanced anti-type 2 diabetes synergy effects
description	Shao-Jun Zhao,1,2,* De-Hua Wang,1,2 Yan-Wei Li,1,2 Lei Han,1,2 Xing Xiao,1,2 Min Ma,3,* David Chi-Cheong Wan,4 An Hong,1,2 Yi Ma1,2 1Institute of Biomedicine, Department of Cellular Biology, Jinan University, 2National Engineering Research Center of Genetic Medicine, Key Laboratory of Bioengineering Medicine of Guangdong Province, Jinan University, 3College of traditional Chinese Medicine, Institute of Integrated Traditional Chinese and Western Medicine, Jinan University, Guangdong, 4School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, People’s Republic of China *These authors contributed equally to this work Abstract: 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 H2O2-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. Keywords: pituitary adenylate cyclase activating peptide (PACAP)-derived peptide, nano-selenium, VPAC2 receptor, synergy effect, type 2 diabetes (T2D)
format	article
author	Zhao SJ Wang DH Li YW Han L Xiao X Ma M Wan DC Hong A Ma Y
author_facet	Zhao SJ Wang DH Li YW Han L Xiao X Ma M Wan DC Hong A Ma Y
author_sort	Zhao SJ
title	A novel selective VPAC2 agonist peptide-conjugated chitosan modified selenium nanoparticles with enhanced anti-type 2 diabetes synergy effects
title_short	A novel selective VPAC2 agonist peptide-conjugated chitosan modified selenium nanoparticles with enhanced anti-type 2 diabetes synergy effects
title_full	A novel selective VPAC2 agonist peptide-conjugated chitosan modified selenium nanoparticles with enhanced anti-type 2 diabetes synergy effects
title_fullStr	A novel selective VPAC2 agonist peptide-conjugated chitosan modified selenium nanoparticles with enhanced anti-type 2 diabetes synergy effects
title_full_unstemmed	A novel selective VPAC2 agonist peptide-conjugated chitosan modified selenium nanoparticles with enhanced anti-type 2 diabetes synergy effects
title_sort	novel selective vpac2 agonist peptide-conjugated chitosan modified selenium nanoparticles with enhanced anti-type 2 diabetes synergy effects
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/2c4da66d5a8f49aeb79eb0c9e773df2a
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A novel selective VPAC2 agonist peptide-conjugated chitosan modified selenium nanoparticles with enhanced anti-type 2 diabetes synergy effects

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