DC260126: a small-molecule antagonist of GPR40 that protects against pancreatic β-Cells dysfunction in db/db mice.

G protein-coupled receptor 40 (GPR40) mediates both acute and chronic effects of free fatty acids (FFAs) on insulin secretion. However, it remains controversial whether inhibition of GPR40 would be beneficial in prevention of type 2 diabetes. This study is designed to evaluate the potential effects...

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Autores principales:	Peng Sun, Ting Wang, Yuren Zhou, Hong Liu, Hualiang Jiang, Weiliang Zhu, Heyao Wang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a53542f5ffd74f059489f804e6d9ee9a
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spelling	oai:doaj.org-article:a53542f5ffd74f059489f804e6d9ee9a2021-11-18T07:42:11ZDC260126: a small-molecule antagonist of GPR40 that protects against pancreatic β-Cells dysfunction in db/db mice.1932-620310.1371/journal.pone.0066744https://doaj.org/article/a53542f5ffd74f059489f804e6d9ee9a2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23776696/?tool=EBIhttps://doaj.org/toc/1932-6203G protein-coupled receptor 40 (GPR40) mediates both acute and chronic effects of free fatty acids (FFAs) on insulin secretion. However, it remains controversial whether inhibition of GPR40 would be beneficial in prevention of type 2 diabetes. This study is designed to evaluate the potential effects of DC260126, a small molecule antagonist of GPR40, on β-cell function following administration of 10 mg/kg dose of DC260126 to obese diabetic db/db mice. Oral glucose tolerance test, glucose stimulated insulin secretion and insulin tolerance test were used to investigate the pharmacological effects of DC260126 on db/db mice after 21-days treatment. Immunohistochemistry and serum biochemical analysis were also performed in this study. Although no significant change of blood glucose levels was found in DC260126-treated mice, DC260126 significantly inhibited glucose stimulated insulin secretion, reduced blood insulin level and improved insulin sensitivity after 3 weeks administration in db/db mice. Moreover, DC260126 reduced the proinsulin/insulin ratio and the apoptotic rate of pancreatic β-cells remarkably in DC260126-treated db/db mice compared to vehicle-treated mice (p<0.05, n = 8). The results suggest that although DC260126 could not provide benefit for improving hyperglycemia, it could protect against pancreatic β-cells dysfunction through reducing overload of β-cells, and it increases insulin sensitivity possibly via alleviation of hyperinsulinemia in db/db mice.Peng SunTing WangYuren ZhouHong LiuHualiang JiangWeiliang ZhuHeyao WangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 6, p e66744 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Peng Sun Ting Wang Yuren Zhou Hong Liu Hualiang Jiang Weiliang Zhu Heyao Wang DC260126: a small-molecule antagonist of GPR40 that protects against pancreatic β-Cells dysfunction in db/db mice.
description	G protein-coupled receptor 40 (GPR40) mediates both acute and chronic effects of free fatty acids (FFAs) on insulin secretion. However, it remains controversial whether inhibition of GPR40 would be beneficial in prevention of type 2 diabetes. This study is designed to evaluate the potential effects of DC260126, a small molecule antagonist of GPR40, on β-cell function following administration of 10 mg/kg dose of DC260126 to obese diabetic db/db mice. Oral glucose tolerance test, glucose stimulated insulin secretion and insulin tolerance test were used to investigate the pharmacological effects of DC260126 on db/db mice after 21-days treatment. Immunohistochemistry and serum biochemical analysis were also performed in this study. Although no significant change of blood glucose levels was found in DC260126-treated mice, DC260126 significantly inhibited glucose stimulated insulin secretion, reduced blood insulin level and improved insulin sensitivity after 3 weeks administration in db/db mice. Moreover, DC260126 reduced the proinsulin/insulin ratio and the apoptotic rate of pancreatic β-cells remarkably in DC260126-treated db/db mice compared to vehicle-treated mice (p<0.05, n = 8). The results suggest that although DC260126 could not provide benefit for improving hyperglycemia, it could protect against pancreatic β-cells dysfunction through reducing overload of β-cells, and it increases insulin sensitivity possibly via alleviation of hyperinsulinemia in db/db mice.
format	article
author	Peng Sun Ting Wang Yuren Zhou Hong Liu Hualiang Jiang Weiliang Zhu Heyao Wang
author_facet	Peng Sun Ting Wang Yuren Zhou Hong Liu Hualiang Jiang Weiliang Zhu Heyao Wang
author_sort	Peng Sun
title	DC260126: a small-molecule antagonist of GPR40 that protects against pancreatic β-Cells dysfunction in db/db mice.
title_short	DC260126: a small-molecule antagonist of GPR40 that protects against pancreatic β-Cells dysfunction in db/db mice.
title_full	DC260126: a small-molecule antagonist of GPR40 that protects against pancreatic β-Cells dysfunction in db/db mice.
title_fullStr	DC260126: a small-molecule antagonist of GPR40 that protects against pancreatic β-Cells dysfunction in db/db mice.
title_full_unstemmed	DC260126: a small-molecule antagonist of GPR40 that protects against pancreatic β-Cells dysfunction in db/db mice.
title_sort	dc260126: a small-molecule antagonist of gpr40 that protects against pancreatic β-cells dysfunction in db/db mice.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/a53542f5ffd74f059489f804e6d9ee9a
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DC260126: a small-molecule antagonist of GPR40 that protects against pancreatic β-Cells dysfunction in db/db mice.

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