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Low dose doxycycline decreases systemic inflammation and improves glycemic control, lipid profiles, and islet morphology and function in db/db mice

The aim of this study was to determine whether low dose doxycycline as an anti-inflammatory agent could improve glucose metabolism in diabetic animals. Therefore, doxycycline was supplemented in drinking water to 6-week-old male db/db mice for 10 weeks. Doxycycline reduced perirenal/epididymal fat,...

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Autores principales: Wang, Na, Tian, Xiong, Chen, Yu, Tan, Hui-qi, Xie, Pei-jian, Chen, Shao-jun, Fu, Yu-cai, Chen, Yi-xin, Xu, Wen-can, Wei, Chi-ju
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5666019/
https://www.ncbi.nlm.nih.gov/pubmed/29089617
http://dx.doi.org/10.1038/s41598-017-14408-7
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author Wang, Na
Tian, Xiong
Chen, Yu
Tan, Hui-qi
Xie, Pei-jian
Chen, Shao-jun
Fu, Yu-cai
Chen, Yi-xin
Xu, Wen-can
Wei, Chi-ju
author_facet Wang, Na
Tian, Xiong
Chen, Yu
Tan, Hui-qi
Xie, Pei-jian
Chen, Shao-jun
Fu, Yu-cai
Chen, Yi-xin
Xu, Wen-can
Wei, Chi-ju
author_sort Wang, Na
collection PubMed
description The aim of this study was to determine whether low dose doxycycline as an anti-inflammatory agent could improve glucose metabolism in diabetic animals. Therefore, doxycycline was supplemented in drinking water to 6-week-old male db/db mice for 10 weeks. Doxycycline reduced perirenal/epididymal fat, Lee’s index, and liver cholesterol. Blood HDL-cholesterol increased, but total cholesterol and aspartate transaminase decreased. Glucose and insulin tolerances were improved, accompanying with reduced fasting blood glucose, insulin, HOMA-IR and advanced glycation end products. Islet number, β-cell percentage and mass increased, while islet size decreased. Consistently, less apoptosis but more β-cell proliferation were found in islets of treated mice. Freshly isolated islets from treated mice showed higher insulin content and enhanced glucose stimulated insulin secretion (GSIS). In addition, purified islets of Balb/c mice showed increased GSIS after cultivation in vitro with doxycycline, but not with chloramphenicol and levofloxacin. Inflammation markers, including lipopolysaccharides (LPS) and C-reactive protein (CRP) in serum as well as CD68-positive cells in treated islets, decreased significantly. Finally, LPS stimulated the production of inflammatory factors but inhibited GSIS of MIN6 cells; however, the effects were completely reversed by doxycycline. The results support further study of possible long-term usage of sub-antimicrobial doxycycline in diabetic patients.
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spelling pubmed-56660192017-11-08 Low dose doxycycline decreases systemic inflammation and improves glycemic control, lipid profiles, and islet morphology and function in db/db mice Wang, Na Tian, Xiong Chen, Yu Tan, Hui-qi Xie, Pei-jian Chen, Shao-jun Fu, Yu-cai Chen, Yi-xin Xu, Wen-can Wei, Chi-ju Sci Rep Article The aim of this study was to determine whether low dose doxycycline as an anti-inflammatory agent could improve glucose metabolism in diabetic animals. Therefore, doxycycline was supplemented in drinking water to 6-week-old male db/db mice for 10 weeks. Doxycycline reduced perirenal/epididymal fat, Lee’s index, and liver cholesterol. Blood HDL-cholesterol increased, but total cholesterol and aspartate transaminase decreased. Glucose and insulin tolerances were improved, accompanying with reduced fasting blood glucose, insulin, HOMA-IR and advanced glycation end products. Islet number, β-cell percentage and mass increased, while islet size decreased. Consistently, less apoptosis but more β-cell proliferation were found in islets of treated mice. Freshly isolated islets from treated mice showed higher insulin content and enhanced glucose stimulated insulin secretion (GSIS). In addition, purified islets of Balb/c mice showed increased GSIS after cultivation in vitro with doxycycline, but not with chloramphenicol and levofloxacin. Inflammation markers, including lipopolysaccharides (LPS) and C-reactive protein (CRP) in serum as well as CD68-positive cells in treated islets, decreased significantly. Finally, LPS stimulated the production of inflammatory factors but inhibited GSIS of MIN6 cells; however, the effects were completely reversed by doxycycline. The results support further study of possible long-term usage of sub-antimicrobial doxycycline in diabetic patients. Nature Publishing Group UK 2017-10-31 /pmc/articles/PMC5666019/ /pubmed/29089617 http://dx.doi.org/10.1038/s41598-017-14408-7 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Wang, Na
Tian, Xiong
Chen, Yu
Tan, Hui-qi
Xie, Pei-jian
Chen, Shao-jun
Fu, Yu-cai
Chen, Yi-xin
Xu, Wen-can
Wei, Chi-ju
Low dose doxycycline decreases systemic inflammation and improves glycemic control, lipid profiles, and islet morphology and function in db/db mice
title Low dose doxycycline decreases systemic inflammation and improves glycemic control, lipid profiles, and islet morphology and function in db/db mice
title_full Low dose doxycycline decreases systemic inflammation and improves glycemic control, lipid profiles, and islet morphology and function in db/db mice
title_fullStr Low dose doxycycline decreases systemic inflammation and improves glycemic control, lipid profiles, and islet morphology and function in db/db mice
title_full_unstemmed Low dose doxycycline decreases systemic inflammation and improves glycemic control, lipid profiles, and islet morphology and function in db/db mice
title_short Low dose doxycycline decreases systemic inflammation and improves glycemic control, lipid profiles, and islet morphology and function in db/db mice
title_sort low dose doxycycline decreases systemic inflammation and improves glycemic control, lipid profiles, and islet morphology and function in db/db mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5666019/
https://www.ncbi.nlm.nih.gov/pubmed/29089617
http://dx.doi.org/10.1038/s41598-017-14408-7
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