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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3568082/ https://www.ncbi.nlm.nih.gov/pubmed/23409091 http://dx.doi.org/10.1371/journal.pone.0055925 |
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author | Akash, Muhammad Sajid Hamid Rehman, Kanwal Sun, Hongying Chen, Shuqing |
author_facet | Akash, Muhammad Sajid Hamid Rehman, Kanwal Sun, Hongying Chen, Shuqing |
author_sort | Akash, Muhammad Sajid Hamid |
collection | PubMed |
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 | Online Article Text |
id | pubmed-3568082 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35680822013-02-13 Sustained Delivery of IL-1Ra from PF127-Gel Reduces Hyperglycemia in Diabetic GK-Rats Akash, Muhammad Sajid Hamid Rehman, Kanwal Sun, Hongying Chen, Shuqing PLoS One Research Article 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. Public Library of Science 2013-02-08 /pmc/articles/PMC3568082/ /pubmed/23409091 http://dx.doi.org/10.1371/journal.pone.0055925 Text en © 2013 Akash et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Akash, Muhammad Sajid Hamid Rehman, Kanwal Sun, Hongying Chen, Shuqing Sustained Delivery of IL-1Ra from PF127-Gel Reduces Hyperglycemia in Diabetic GK-Rats |
title | 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_short | 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 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3568082/ https://www.ncbi.nlm.nih.gov/pubmed/23409091 http://dx.doi.org/10.1371/journal.pone.0055925 |
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