Hepatic p38 alpha regulates gluconeogenesis by suppressing AMPK
文献类型：期刊论文
| 作者 | Jing, YY; Liu, W; Cao, HC; Zhang, D; Yao, X; Zhang, SJ; Xia, HF; Li, D; Wang, YC; Yan, J |
| 刊名 | JOURNAL OF HEPATOLOGY
 |
| 出版日期 | 2015 |
| 卷号 | 62期号:6页码:1319-1327 |
| 关键词 | p38 alpha Gluconeogenesis AMPK TAK1 Energy state |
| 通讯作者 | Ying, H (reprint author), Chinese Acad Sci, SIBS, INS, 320 Yueyang Rd, Shanghai 200031, Peoples R China.,yinghao@sibs.ac.cn |
| 英文摘要 | Background & Aims: It is proposed that p38 is involved in gluconeogenesis, however, the genetic evidence is lacking and precise mechanisms remain poorly understood. We sought to delineate the role of hepatic p38 alpha in gluconeogenesis during fasting by applying a loss-of-function genetic approach. Methods: We examined fasting glucose levels, performed pyruvate tolerance test, imaged G6Pase promoter activity, as well as determined the expression of gluconeogenic genes in mice with a targeted deletion of p38a in liver. Results were confirmed both in vivo and in vitro by using an adenoviral dominant-negative form of p38 alpha (p38 alpha-AF) and the constitutively active mitogenactivated protein kinase 6, respectively. Adenoviral dominantnegative form of AMP-activated protein kinase alpha (DN-AMPK alpha) was employed to test our proposed model. Results: Mice lacking hepatic p38a exhibited reduced fasting glucose level and impaired gluconeogenesis. Interestingly, hepatic deficiency of p38 alpha did not result in an alteration in CREB phosphorylation, but led to an increase in AMPK alpha phosphorylation. Adenoviral DN-AMPK alpha could abolish the effect of p38 alpha-AF on gluconeogenesis. Knockdown of up-steam transforming growth factor beta-activated kinase 1 decreased the AMPKa phosphorylation induced by p38 alpha-AF, suggesting a negative feedback loop. Consistently, inverse correlations between p38 and AMPKa phosphorylation were observed during fasting and in diabetic mouse models. Importantly, adenoviral p38 alpha-AF treatment ameliorated hyperglycemia in diabetic mice. |
| 学科主题 | Gastroenterology & Hepatology |
| 类目[WOS] | Gastroenterology & Hepatology |
| 关键词[WOS] | ACTIVATED PROTEIN-KINASE ; GLUCOSE-PRODUCTION ; ENERGY-SENSOR ; LIVER ; INSULIN ; TAK1 ; HOMEOSTASIS ; METABOLISM ; GLUCAGON ; RECEPTOR |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000354574800015 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/75]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Jing, YY,Liu, W,Cao, HC,et al. Hepatic p38 alpha regulates gluconeogenesis by suppressing AMPK[J]. JOURNAL OF HEPATOLOGY,2015,62(6):1319-1327. |
| APA | Jing, YY.,Liu, W.,Cao, HC.,Zhang, D.,Yao, X.,...&Ying, H.(2015).Hepatic p38 alpha regulates gluconeogenesis by suppressing AMPK.JOURNAL OF HEPATOLOGY,62(6),1319-1327. |
| MLA | Jing, YY,et al."Hepatic p38 alpha regulates gluconeogenesis by suppressing AMPK".JOURNAL OF HEPATOLOGY 62.6(2015):1319-1327. |
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