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Dexamethasone-induced Kruppel-like factor 9 expression promotes hepatic gluconeogenesis and hyperglycemia 期刊论文

编号：

61514454-d49c-4b06-aee9-2ad2062beb8a
作者：

Cui, Anfang^[1,2];Fan, Heng^[1,2];Zhang, Yinliang^[1,2];Zhang, Yujie^[1,2];Niu, Dong^[1,2];Liu, Shuainan^[2,3];Liu, Quan^[2,3];Ma, Wei^[4];Shen, Zhufang^[2,3];Shen, Lian^[1,2];Liu, Yanling;Zhang, Huabing^[1,2];Xue, Yuan^[1,2];Cui, Ying^[1,2];Wang, Qinghua(王庆华)^[5]Xiao, Xinhua^[6];Fang, Fude^[1,2];Yang, Jichun^[4];Cui, Qinghua^[4];Chang, Yongsheng^[1,2,7];
语种：

英文
期刊：

JOURNAL OF CLINICAL INVESTIGATION ISSN：0021-9738 2019 年 129 卷 6 期 (2266 - 2278) ; JUN 3
收录：
摘要：

Chronic glucocorticoid therapy has serious side effects, including diabetes and fatty liver. However, the molecular mechanisms responsible for steroid-induced diabetes remain largely enigmatic. Here, we show that hepatic Kruppel-like factor 9 (Klf9) gene expression is induced by dexamethasone and fasting. The overexpression of Klf9 in primary hepatocytes strongly stimulated Pgc1a gene expression through direct binding to its promoter, thereby activating the gluconeogenic program. However, Klf9 mutation abolished the stimulatory effect of dexamethasone on cellular glucose output. Adenovirus-mediated overexpression of KLF9 in the mouse liver markedly increased blood glucose levels and impaired glucose tolerance. Conversely, both global Klf9-mutant mice and liver-specific Klf9-deleted mice displayed fasting hypoglycemia. Moreover, the knockdown of Klf9 in the liver in diabetic mouse models, including ob/ob and db/db mice, markedly lowered fasting blood glucose levels. Notably, hepatic Klf9 deficiency in mice alleviated hyperglycemia induced by chronic dexamethasone treatment. These results suggest a critical role for KLF9 in the regulation of hepatic glucose metabolism and identify hepatic induction of KLF9 as a mechanism underlying glucocorticoid therapy-induced diabetes.
推荐引用方式
GB/T 7714：

Cui Anfang,Fan Heng,Zhang Yinliang, et al. Dexamethasone-induced Kruppel-like factor 9 expression promotes hepatic gluconeogenesis and hyperglycemia [J].JOURNAL OF CLINICAL INVESTIGATION,2019,129(6):2266-2278.
APA：

Cui Anfang,Fan Heng,Zhang Yinliang,Zhang Yujie,&Chang Yongsheng.(2019).Dexamethasone-induced Kruppel-like factor 9 expression promotes hepatic gluconeogenesis and hyperglycemia .JOURNAL OF CLINICAL INVESTIGATION,129(6):2266-2278.
MLA：

Cui Anfang, et al. "Dexamethasone-induced Kruppel-like factor 9 expression promotes hepatic gluconeogenesis and hyperglycemia" .JOURNAL OF CLINICAL INVESTIGATION 129,6(2019):2266-2278.
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