The potential insulin sensitizing and glucose lowering effects of a novel indole derivative in vitro and in vivo

doi:10.1016/j.phrs.2007.08.002

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	The potential insulin sensitizing and glucose lowering effects of a novel indole derivative in vitro and in vivo
	Li, Ying-Yin ; Wu, Hao-Shu ; Tang, Lei ; Feng, Chu-Rui ; Yu, Juan-Hong ; Li, Yu ; Yang, Yu-She; Yang, Bo ; He, Qiao-Jun
刊名	PHARMACOLOGICAL RESEARCH
	2007-10
卷号	56 期号:4 页码:335-343
关键词	GY3 insulin sensitizing adipocytokines antidiabetes
ISSN号	1043-6618
DOI	10.1016/j.phrs.2007.08.002
文献子类	Article
英文摘要	Thiazolidinediones (TZDs) such as rosiglitazone are antidiabetic peroxisome proliferator-activated receptor gamma (PPAR gamma) agonists. PTAR gamma agents improve diabetes by increasing insulin sensitivity and enhancing the differentiation of preadipocytes into adipocytes. The present study aimed to identify if 1-(4-chlorobenzoyl)-5-hydroxy-2-methyl-3-indoleacetitic acid (GY3), a newly synthesized indole compound, could enhance adipocytes differentiation and insulin sensitivity. The results showed that both GY3 and rosiglitazone significantly increased the lipid accumulating of 3T3-L1 adipocytes induced by isobutylmethylxanthine, dexamethasone and insulin mixture, but GY3 (not rosiglitazone) failed to increase the lipid accumulation when induced by insulin alone. In addition, GY3- or rosiglitaozne-induced protein expression of GLUT4 and adiponectin was determined by Western blot analysis. GY3 activated PPAR alpha weakly but did not affect PPAR gamma, while rosiglitazone activated PPAR gamma significantly, suggesting different mechanisms between GY3 and rosiglitazone on adipocyte differentiation. Furthermore, both GY3 and rosialitazone enhanced the adiponectin and insulin pathway proteins expression and adiponectin secretion in mature adipocytes, but only GY3 not rosiglitazone elevated gene expression of leptin and resistin. Both GY3 and rosiglitazone enhanced glucose consumption in HepG2 cells especially in the presence of insulin. In the in vivo study, GY3 decreased serum glucose and insulin in db/db mice, indicating the insulin sensitizing effect might contribute to its antidiabetic mechanism. Altogether, these results suggest that GY3 could improve insulin resistance and lower glucose level, GY3 and its derivatives might be developed as a substitution therapy for diseases with insulin resistance. (c) 2007 Elsevier Ltd. All rights reserved.
WOS关键词	RECEPTOR-GAMMA AGONISTS ; ADIPOSE-TISSUE ; RESISTIN EXPRESSION ; METABOLIC SYNDROME ; DIABETIC-PATIENTS ; PPAR-GAMMA ; OBESITY ; ADIPONECTIN ; ADIPOCYTE ; MICE
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
WOS记录号	WOS:000250617100008
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/273144]
专题	新药研究国家重点实验室中科院受体结构与功能重点实验室
通讯作者	He, Qiao-Jun
作者单位	1.Guiyang Med Coll, Sch Pharm, Guiyang 550004, Peoples R China 2.Zhejiang Univ, Coll Pharmaceut Sci, Inst Pharmacol & Toxicol & Biochem Pharmaceut, Hangzhou 310058, Zhejiang, Peoples R China 3.Chinese Acad Sci, Grad Sch, Shanghai Inst Biol Sci, Shanghai Inst Mat Med,State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Li, Ying-Yin,Wu, Hao-Shu,Tang, Lei,et al. The potential insulin sensitizing and glucose lowering effects of a novel indole derivative in vitro and in vivo[J]. PHARMACOLOGICAL RESEARCH,2007,56(4):335-343.
APA	Li, Ying-Yin.,Wu, Hao-Shu.,Tang, Lei.,Feng, Chu-Rui.,Yu, Juan-Hong.,...&He, Qiao-Jun.(2007).The potential insulin sensitizing and glucose lowering effects of a novel indole derivative in vitro and in vivo.PHARMACOLOGICAL RESEARCH,56(4),335-343.
MLA	Li, Ying-Yin,et al."The potential insulin sensitizing and glucose lowering effects of a novel indole derivative in vitro and in vivo".PHARMACOLOGICAL RESEARCH 56.4(2007):335-343.