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学科主题: 基础医学
题名:
Thiazolidinediones attenuate lipolysis and ameliorate dexamethasone-induced insulin resistance
作者: He, Jinhan1; Xu, Chong2; Kuang, Jiangying1; Liu, Qinhui1; Jiang, Hongfeng3; Mo, Li; Geng, Bin; Xu, Guoheng3
关键词: Thiazolidinedione ; Lipolysis ; Free fatty acids ; Dexamethasone ; Insulin resistance
刊名: METABOLISM-CLINICAL AND EXPERIMENTAL
发表日期: 2015-07-01
DOI: 10.1016/j.metabol.2015.02.005
卷: 64, 期:7, 页:826-836
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Endocrinology & Metabolism
研究领域[WOS]: Endocrinology & Metabolism
关键词[WOS]: NECROSIS-FACTOR-ALPHA ; ADIPOSE TRIGLYCERIDE LIPASE ; ACTIVATED RECEPTOR-GAMMA ; PRIMARY RAT ADIPOCYTES ; HORMONE-SENSITIVE LIPASE ; ACID TRANSPORT PROTEIN ; FREE FATTY-ACIDS ; PPAR-GAMMA ; IN-VIVO ; PHOSPHATIDYLINOSITOL 3-KINASE
英文摘要:

Background. Elevated levels of circulating free fatty acids induce insulin resistance and often occur in obese and diabetic conditions. One pharmacological basis for the antidiabetic effects of thiazolidinediones (TZDs) is that TZDs reduce levels of circulating FFAs by accelerating their uptake and reesterification from plasma into adipocytes. Here, we investigated whether TZDs affect adipose lipolysis, a process controlling triglyceride hydrolysis and FFA efflux to the bloodstream.

Methods. The effects of TZDs on lipolysis were investigated in primary rat adipocytes in vitro and in rats in vivo.

Results. In rat primary adipocytes, the TZDs pioglitazone, rosiglitazone and troglitazone inhibited the lipolytic reaction dose- and time-dependently and in a post-receptor pathway by decreasing cAMP level and total lipase activity. TZDs increased the phosphorylation of Akt/protein kinase B, an action required for activating cyclic-nucleotide phosphodiesterase 38, a major enzyme responsible for cAMP hydrolysis in adipocytes. Furthermore, rosiglitazone inhibited the lipolytic action in dexamethasone-stimulated adipocytes, thereby preventing the increased level of circulating FFAs, and ameliorated insulin resistance in vivo in dexamethasone-treated rats.

Conclusions. TZDs may attenuate lipolysis and FFA efflux by activating Akt signaling to decrease cAMP level and hence reduce lipase activity in adipocytes. Inhibiting lipolysis and FFA efflux with TZDs could be a pharmacological basis by which TZDs antagonize diabetes, particularly in patients with hypercortisolemia or glucocorticoid challenge. (C) 2015 Elsevier Inc. All rights reserved.

语种: 英语
所属项目编号: 81270926 ; 81471068 ; 91439119 ; 2012CB517505 ; 2012CB517806
项目资助者: National Science Foundation of China ; National Basic Research Program of China
WOS记录号: WOS:000355239800008
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内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/60371
Appears in Collections:基础医学院_期刊论文

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作者单位: 1.Sichuan Univ, West China Hosp, Dept Pharm, State Key Lab Biotherapy, Chengdu 610064, Sichuan, Peoples R China
2.Astronaut Res & Training Ctr China, Beijing 100094, Peoples R China
3.Peking Univ, Sch Basic Med Sci, Dept Physiol & Pathophysiol, Beijing 100191, Peoples R China

Recommended Citation:
He, Jinhan,Xu, Chong,Kuang, Jiangying,et al. Thiazolidinediones attenuate lipolysis and ameliorate dexamethasone-induced insulin resistance[J]. METABOLISM-CLINICAL AND EXPERIMENTAL,2015,64(7):826-836.
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