11 beta- Hydroxysteroid Dehydrogenase Type 1(11 beta-HSD1) mediates insulin resistance through JNK activation in adipocytes

doi:10.1038/srep37160

科研成果详情

题名	11 beta- Hydroxysteroid Dehydrogenase Type 1(11 beta-HSD1) mediates insulin resistance through JNK activation in adipocytes
作者	Peng, Kesong1,2; Pan, Yong 1; Li, Jieli 1; Khan, Zia 3; Fan, Mendi 2; Yin, Haimin 1,2; Tong, Chao 1; Zhao, Yunjie1; Liang, Guang1; Zheng, Chao1,2
发表日期	2016-11-14
发表期刊	SCIENTIFIC REPORTS 影响因子和分区
语种	英语
原始文献类型	Article
其他关键词	PROTEIN-KINASE-C ; JUN NH2-TERMINAL KINASE ; N-TERMINAL KINASE ; ACID-BINDING PROTEIN ; 11-BETA-HYDROXYSTEROID DEHYDROGENASE ; ADIPOSE-TISSUE ; METABOLIC SYNDROME ; GLUCOCORTICOID ACTION ; 3T3-L1 ADIPOCYTES ; EPITHELIAL-CELLS
摘要	Glucocorticoids are used to treat a number of human diseases but often lead to insulin resistance and metabolic syndrome. 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) is a key enzyme that catalyzes the intracellular conversion of cortisone to physiologically active cortisol. Despite the known role of 11 beta-HSD1 and active glucocorticoid in causing insulin resistance, the molecular mechanisms by which insulin resistance is induced remain elusive. The aim of this study is to identify these mechanisms in high fat diet (HFD) experimental models. Mice on a HFD were treated with 11 beta-HSD1 inhibitor as well as a JNK inhibitor. We then treated 3T3-L1-derived adipocytes with prednisone, a synthetic glucocorticoid, and cells with 11 beta-HSD1 overexpression to study insulin resistance. Our results show that 11 beta-HSD1 and JNK inhibition mitigated insulin resistance in HFD mice. Prednisone stimulation or overexpression of 11 beta-HSD1 also caused JNK activation in cultured adipocytes. Inhibition of 11 beta-HSD1 blocked the activation of JNK in adipose tissue of HFD mice as well as in cultured adipocytes. Furthermore, prednisone significantly impaired the insulin signaling pathway, and these effects were reversed by 11 beta-HSD1 and JNK inhibition. Our study demonstrates that glucocorticoid-induced insulin resistance was dependent on 11 beta-HSD1, resulting in the critical activation of JNK signaling in adipocytes.
资助项目	Natural Science Funding of China [81200630, 81500291, 81300678, 21572166, 81302821]; Zhejiang Natural Science Funding [LQ13H310002, LQ12H07001]; Wenzhou Science and Technology Bureau Funding [H20150001]
出版者	NATURE PUBLISHING GROUP
出版地	LONDON
ISSN	2045-2322
卷号	6 页码:37160
DOI	10.1038/srep37160
页数	10
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
WOS记录号	WOS:000387854000001
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	27841334
PMC记录号	PMC5107914
SCOPUSEID	2-s2.0-84995403790
通讯作者地址	[Liang, Guang]Chemical Biology Research Center,School of Pharmaceutical Science,Wenzhou Medical University,Wenzhou, Zhejiang,China
Scopus学科分类	Multidisciplinary
引用统计	被引频次：12[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/18474
专题	药学院（分析测试中心）附属第二医院第二临床医学院、附属第二医院、育英儿童医院药学院（分析测试中心）_生物有机与药物化学研究中心
通讯作者	Liang, Guang
作者单位	1.Chemical Biology Research Center,School of Pharmaceutical Science,Wenzhou Medical University,Wenzhou, Zhejiang,China; 2.Diabetes Center,Department of Endocrinology,Second Affiliated Hospital,Wenzhou Medical University,Wenzhou, Zhejiang,China; 3.Department of Pathology and Laboratory Medicine,Western University,London,N6A5C1,Canada
第一作者单位	生物有机与药物化学研究中心; 附属第二医院
通讯作者单位	生物有机与药物化学研究中心
第一作者的第一单位	生物有机与药物化学研究中心
推荐引用方式 GB/T 7714	Peng, Kesong,Pan, Yong,Li, Jieli,et al. 11 beta- Hydroxysteroid Dehydrogenase Type 1(11 beta-HSD1) mediates insulin resistance through JNK activation in adipocytes[J]. SCIENTIFIC REPORTS,2016,6:37160.
APA	Peng, Kesong., Pan, Yong., Li, Jieli., Khan, Zia., Fan, Mendi., ... & Zheng, Chao. (2016). 11 beta- Hydroxysteroid Dehydrogenase Type 1(11 beta-HSD1) mediates insulin resistance through JNK activation in adipocytes. SCIENTIFIC REPORTS, 6, 37160.
MLA	Peng, Kesong,et al."11 beta- Hydroxysteroid Dehydrogenase Type 1(11 beta-HSD1) mediates insulin resistance through JNK activation in adipocytes".SCIENTIFIC REPORTS 6(2016):37160.