Sustained delivery of IL-1Ra from PF127-gel reduces hyperglycemia in diabetic GK-rats.

Interleukin-1beta (IL-1β) is a major cause for induction of various inflammatory mechanisms that are decisively involved to provoke pathogenesis of type 2 diabetes mellitus (T2DM). Interleukin-1 receptor antagonist (IL-1Ra) a naturally occurring anti-inflammatory antagonist of IL-1β has been recentl...

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Autores principales:	Muhammad Sajid Hamid Akash, Kanwal Rehman, Hongying Sun, Shuqing Chen
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d0ff3e78ab334979b5d5c7e84a5d565e
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spelling	oai:doaj.org-article:d0ff3e78ab334979b5d5c7e84a5d565e2021-11-18T07:58:09ZSustained delivery of IL-1Ra from PF127-gel reduces hyperglycemia in diabetic GK-rats.1932-620310.1371/journal.pone.0055925https://doaj.org/article/d0ff3e78ab334979b5d5c7e84a5d565e2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23409091/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Interleukin-1beta (IL-1β) is a major cause for induction of various inflammatory mechanisms that are decisively involved to provoke pathogenesis of type 2 diabetes mellitus (T2DM). Interleukin-1 receptor antagonist (IL-1Ra) a naturally occurring anti-inflammatory antagonist of IL-1β has been recently approved for treatment of T2DM but due to its short half-life, higher doses and frequent dosing intervals are required. Pluronic F-127 (PF127) has previously shown to prolong the release of various proteinous drugs and their serum half-lives. Subsequently, in our previous work, we developed a new dosage form of IL-1Ra using PF127 and investigated its in-vitro and in-vivo effects. Here in present work, we have extended this approach using diabetic Goto-kakizaki (GK) rats. We administered IL-1Ra loaded in PF127 gel subcutaneously for one month into GK rats. IL-1Ra loaded in PF127 gel exhibited a sustained and prolonged hypoglycemic effects on treated animals. Intraperitoneal glucose tolerance test (IPGTT) results showed that IL-1Ra loaded in PF127 gel increased glucose tolerance along with increased insulin sensitivity and β-cell's secretory function in treated rats. Moreover, significant reduction in pro-insulin/insulin ratio, lipid profiles and interleukin 6 (IL-6) were also observed. Immunohistochemical analysis showed slight macrophages infiltration in pancreatic islets. Histochemical analysis revealed no PF127-induced alteration in the normal physiology of skin and kidney of treated animals. Hence, we concluded that IL-1Ra loaded in PF127 gel has potential to exhibit broad spectrum anti-inflammatory effects alleviating the symptoms of T2DM.Muhammad Sajid Hamid AkashKanwal RehmanHongying SunShuqing ChenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 2, p e55925 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Muhammad Sajid Hamid Akash Kanwal Rehman Hongying Sun Shuqing Chen Sustained delivery of IL-1Ra from PF127-gel reduces hyperglycemia in diabetic GK-rats.
description	Interleukin-1beta (IL-1β) is a major cause for induction of various inflammatory mechanisms that are decisively involved to provoke pathogenesis of type 2 diabetes mellitus (T2DM). Interleukin-1 receptor antagonist (IL-1Ra) a naturally occurring anti-inflammatory antagonist of IL-1β has been recently approved for treatment of T2DM but due to its short half-life, higher doses and frequent dosing intervals are required. Pluronic F-127 (PF127) has previously shown to prolong the release of various proteinous drugs and their serum half-lives. Subsequently, in our previous work, we developed a new dosage form of IL-1Ra using PF127 and investigated its in-vitro and in-vivo effects. Here in present work, we have extended this approach using diabetic Goto-kakizaki (GK) rats. We administered IL-1Ra loaded in PF127 gel subcutaneously for one month into GK rats. IL-1Ra loaded in PF127 gel exhibited a sustained and prolonged hypoglycemic effects on treated animals. Intraperitoneal glucose tolerance test (IPGTT) results showed that IL-1Ra loaded in PF127 gel increased glucose tolerance along with increased insulin sensitivity and β-cell's secretory function in treated rats. Moreover, significant reduction in pro-insulin/insulin ratio, lipid profiles and interleukin 6 (IL-6) were also observed. Immunohistochemical analysis showed slight macrophages infiltration in pancreatic islets. Histochemical analysis revealed no PF127-induced alteration in the normal physiology of skin and kidney of treated animals. Hence, we concluded that IL-1Ra loaded in PF127 gel has potential to exhibit broad spectrum anti-inflammatory effects alleviating the symptoms of T2DM.
format	article
author	Muhammad Sajid Hamid Akash Kanwal Rehman Hongying Sun Shuqing Chen
author_facet	Muhammad Sajid Hamid Akash Kanwal Rehman Hongying Sun Shuqing Chen
author_sort	Muhammad Sajid Hamid Akash
title	Sustained delivery of IL-1Ra from PF127-gel reduces hyperglycemia in diabetic GK-rats.
title_short	Sustained delivery of IL-1Ra from PF127-gel reduces hyperglycemia in diabetic GK-rats.
title_full	Sustained delivery of IL-1Ra from PF127-gel reduces hyperglycemia in diabetic GK-rats.
title_fullStr	Sustained delivery of IL-1Ra from PF127-gel reduces hyperglycemia in diabetic GK-rats.
title_full_unstemmed	Sustained delivery of IL-1Ra from PF127-gel reduces hyperglycemia in diabetic GK-rats.
title_sort	sustained delivery of il-1ra from pf127-gel reduces hyperglycemia in diabetic gk-rats.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/d0ff3e78ab334979b5d5c7e84a5d565e
work_keys_str_mv	AT muhammadsajidhamidakash sustaineddeliveryofil1rafrompf127gelreduceshyperglycemiaindiabeticgkrats AT kanwalrehman sustaineddeliveryofil1rafrompf127gelreduceshyperglycemiaindiabeticgkrats AT hongyingsun sustaineddeliveryofil1rafrompf127gelreduceshyperglycemiaindiabeticgkrats AT shuqingchen sustaineddeliveryofil1rafrompf127gelreduceshyperglycemiaindiabeticgkrats
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Sustained delivery of IL-1Ra from PF127-gel reduces hyperglycemia in diabetic GK-rats.

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