Cargando…

The Role of PPARδ Agosnist GW501516 in Rats with Gestational Diabetes Mellitus

BACKGROUND: Gestational diabetes mellitus (GDM) is a disorder of glucose metabolism that occurs or is found for the first time during pregnancy. GDM is very harmful and urgently needs drug treatment to improve pregnancy outcome. PPARδ is involved in a variety of biological processes related to glyco...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhou, Jun, Zhe, Ruilian, Guo, Xiaohui, Chen, Yuying, Zou, Yan, Zhou, Li, Wang, Zhijian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335770/
https://www.ncbi.nlm.nih.gov/pubmed/32669864
http://dx.doi.org/10.2147/DMSO.S251491
_version_ 1783554192985554944
author Zhou, Jun
Zhe, Ruilian
Guo, Xiaohui
Chen, Yuying
Zou, Yan
Zhou, Li
Wang, Zhijian
author_facet Zhou, Jun
Zhe, Ruilian
Guo, Xiaohui
Chen, Yuying
Zou, Yan
Zhou, Li
Wang, Zhijian
author_sort Zhou, Jun
collection PubMed
description BACKGROUND: Gestational diabetes mellitus (GDM) is a disorder of glucose metabolism that occurs or is found for the first time during pregnancy. GDM is very harmful and urgently needs drug treatment to improve pregnancy outcome. PPARδ is involved in a variety of biological processes related to glycolipid metabolism in the body, suggesting that it may be closely related to insulin resistance and impaired glucose tolerance. The role of PPARδ agonist GW501516 in gestational diabetes has not been studied. METHODS: Firstly, the rat model of GDM was established. Then, fasting blood-glucose (FGB), fasting insulin (FINS), HOMA-islet resistance index (HOMA-IR) and insulin sensitivity index (ISI) of GDM rats treated with GW501516 were measured on day 3, day 10 and day 17. Glucose tolerance test was performed on the 20th day of gestation to measure glucose tolerance in rats. The expression of PPARδ and Angptl8 in islet tissues of rats was detected by Western blot and immunohistochemistry (IHC). Histopathological changes of islet were detected by HE stain; apoptosis rate of islet cells was detected by Tunel; and expression of apoptosis-related proteins in the cells was detected by Western blot. The biochemical kits were used to detect the expression of lipid metabolism-related factors in blood of GDM rats after the PPARδ agonist GW501516 treatment. Finally, the expression of SREBP-1c and GLUT2 in islet tissues was detected by RT-qPCR and IHC. RESULTS: The PPARδ agonist GW501516 decreased the expression of FGB, FINS and HOMA-IR in GDM rats, and we found that GW501516 decreased ISI in GDM rats. GW501516 increased glucose tolerance in GDM rats too. In GDM rats, the expression of PPARδ in islet decreased and the expression of Angptl8 increased, which was reversed by GW501516. In addition, we also found that GW501516 can improve the damaged islet tissue of GDM rats, reduce the apoptosis rate of islet cells and inhibit the expression of lipid metabolism-related factors in the blood. Finally, we found that GW501516 inhibited the expression of SREBP-1c and promoted the expression of GLUT2 in the islet tissue. CONCLUSION: The PPARδ agonist GW501516 could improve the blood glucose level, damaged islet tissue and increase the insulin content in the rats with GDM, possibly by regulating the SREBP-1c/GLUT2 pathway. Our study provided a new basis for clinical treatment of GDM in pregnant women with PPARδ agonist GW501516.
format Online
Article
Text
id pubmed-7335770
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Dove
record_format MEDLINE/PubMed
spelling pubmed-73357702020-07-14 The Role of PPARδ Agosnist GW501516 in Rats with Gestational Diabetes Mellitus Zhou, Jun Zhe, Ruilian Guo, Xiaohui Chen, Yuying Zou, Yan Zhou, Li Wang, Zhijian Diabetes Metab Syndr Obes Original Research BACKGROUND: Gestational diabetes mellitus (GDM) is a disorder of glucose metabolism that occurs or is found for the first time during pregnancy. GDM is very harmful and urgently needs drug treatment to improve pregnancy outcome. PPARδ is involved in a variety of biological processes related to glycolipid metabolism in the body, suggesting that it may be closely related to insulin resistance and impaired glucose tolerance. The role of PPARδ agonist GW501516 in gestational diabetes has not been studied. METHODS: Firstly, the rat model of GDM was established. Then, fasting blood-glucose (FGB), fasting insulin (FINS), HOMA-islet resistance index (HOMA-IR) and insulin sensitivity index (ISI) of GDM rats treated with GW501516 were measured on day 3, day 10 and day 17. Glucose tolerance test was performed on the 20th day of gestation to measure glucose tolerance in rats. The expression of PPARδ and Angptl8 in islet tissues of rats was detected by Western blot and immunohistochemistry (IHC). Histopathological changes of islet were detected by HE stain; apoptosis rate of islet cells was detected by Tunel; and expression of apoptosis-related proteins in the cells was detected by Western blot. The biochemical kits were used to detect the expression of lipid metabolism-related factors in blood of GDM rats after the PPARδ agonist GW501516 treatment. Finally, the expression of SREBP-1c and GLUT2 in islet tissues was detected by RT-qPCR and IHC. RESULTS: The PPARδ agonist GW501516 decreased the expression of FGB, FINS and HOMA-IR in GDM rats, and we found that GW501516 decreased ISI in GDM rats. GW501516 increased glucose tolerance in GDM rats too. In GDM rats, the expression of PPARδ in islet decreased and the expression of Angptl8 increased, which was reversed by GW501516. In addition, we also found that GW501516 can improve the damaged islet tissue of GDM rats, reduce the apoptosis rate of islet cells and inhibit the expression of lipid metabolism-related factors in the blood. Finally, we found that GW501516 inhibited the expression of SREBP-1c and promoted the expression of GLUT2 in the islet tissue. CONCLUSION: The PPARδ agonist GW501516 could improve the blood glucose level, damaged islet tissue and increase the insulin content in the rats with GDM, possibly by regulating the SREBP-1c/GLUT2 pathway. Our study provided a new basis for clinical treatment of GDM in pregnant women with PPARδ agonist GW501516. Dove 2020-06-30 /pmc/articles/PMC7335770/ /pubmed/32669864 http://dx.doi.org/10.2147/DMSO.S251491 Text en © 2020 Zhou et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Zhou, Jun
Zhe, Ruilian
Guo, Xiaohui
Chen, Yuying
Zou, Yan
Zhou, Li
Wang, Zhijian
The Role of PPARδ Agosnist GW501516 in Rats with Gestational Diabetes Mellitus
title The Role of PPARδ Agosnist GW501516 in Rats with Gestational Diabetes Mellitus
title_full The Role of PPARδ Agosnist GW501516 in Rats with Gestational Diabetes Mellitus
title_fullStr The Role of PPARδ Agosnist GW501516 in Rats with Gestational Diabetes Mellitus
title_full_unstemmed The Role of PPARδ Agosnist GW501516 in Rats with Gestational Diabetes Mellitus
title_short The Role of PPARδ Agosnist GW501516 in Rats with Gestational Diabetes Mellitus
title_sort role of pparδ agosnist gw501516 in rats with gestational diabetes mellitus
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335770/
https://www.ncbi.nlm.nih.gov/pubmed/32669864
http://dx.doi.org/10.2147/DMSO.S251491
work_keys_str_mv AT zhoujun theroleofppardagosnistgw501516inratswithgestationaldiabetesmellitus
AT zheruilian theroleofppardagosnistgw501516inratswithgestationaldiabetesmellitus
AT guoxiaohui theroleofppardagosnistgw501516inratswithgestationaldiabetesmellitus
AT chenyuying theroleofppardagosnistgw501516inratswithgestationaldiabetesmellitus
AT zouyan theroleofppardagosnistgw501516inratswithgestationaldiabetesmellitus
AT zhouli theroleofppardagosnistgw501516inratswithgestationaldiabetesmellitus
AT wangzhijian theroleofppardagosnistgw501516inratswithgestationaldiabetesmellitus
AT zhoujun roleofppardagosnistgw501516inratswithgestationaldiabetesmellitus
AT zheruilian roleofppardagosnistgw501516inratswithgestationaldiabetesmellitus
AT guoxiaohui roleofppardagosnistgw501516inratswithgestationaldiabetesmellitus
AT chenyuying roleofppardagosnistgw501516inratswithgestationaldiabetesmellitus
AT zouyan roleofppardagosnistgw501516inratswithgestationaldiabetesmellitus
AT zhouli roleofppardagosnistgw501516inratswithgestationaldiabetesmellitus
AT wangzhijian roleofppardagosnistgw501516inratswithgestationaldiabetesmellitus