Prostaglandin F-2 Facilitates Hepatic Glucose Production Through CaMKII/p38/FOXO1 Signaling Pathway in Fasting and Obesity
文献类型：期刊论文
| 作者 | Wang, Yuanyang1; Chen, Guilin1; Liu, Qian1; Shen, Yujun1; Yu, Ying1,5; Yan, Shuai5; Xiao, Bing5; Zuo, Shengkai5; Zhang, Qianqian5; Yu, Yu5 |
| 刊名 | DIABETES
 |
| 出版日期 | 2018 |
| 卷号 | 67期号:9页码:1748-1760 |
| ISSN号 | 0012-1797 |
| DOI | 10.2337/db17-1521 |
| 文献子类 | Article |
| 英文摘要 | Gluconeogenesis is drastically increased in patients with type 2 diabetes and accounts for increased fasting plasma glucose concentrations. Circulating levels of prostaglandin (PG) F-2 are also markedly elevated in diabetes; however, whether and how PGF(2) regulates hepatic glucose metabolism remain unknown. Here, we demonstrated that PGF(2) receptor (F-prostanoid receptor [FP]) was upregulated in the livers of mice upon fasting- and diabetic stress. Hepatic deletion of the FP receptor suppressed fasting-induced hepatic gluconeogenesis, whereas FP overexpression enhanced hepatic gluconeogenesis in mice. FP activation promoted the expression of gluconeogenic enzymes (PEPCK and glucose-6-phosphatase) in hepatocytes in a FOXO1-dependent manner. Additionally, FP coupled with G(q) in hepatocytes to elicit Ca2+ release, which activated Ca2+/calmodulin-activated protein kinase II (CaMKII) to increase FOXO1 phosphorylation and subsequently accelerate its nuclear translocation. Blockage of p38 disrupted CaMKII-induced FOXO1 nuclear translocation and abrogated FP-mediated hepatic gluconeogenesis in mice. Moreover, knockdown of hepatic FP receptor improved insulin sensitivity and glucose homeostasis in ob/ob mice. FP-mediated hepatic gluconeogenesis via the CaMKII/p38/FOXO1 signaling pathway, indicating that the FP receptor might be a promising therapeutic target for type 2 diabetes. |
| 学科主题 | Endocrinology & Metabolism |
| WOS关键词 | OXIDATIVE STRESS ; RAT-LIVER ; MEDIATED INFLAMMATION ; CARDIOVASCULAR RISK ; ENDOTHELIAL-CELLS ; DOSE ASPIRIN ; IN-VIVO ; GLUCONEOGENESIS ; ACTIVATION ; KINASE |
| 语种 | 英语 |
| 出版者 | AMER DIABETES ASSOC |
| WOS记录号 | WOS:000442337900007 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/701]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Tianjin Med Univ, Key Lab Immune Microenvironm & Dis, Minist Educ,Dept Pharmacol,Sch Basic Med Sci, Collaborat Innovat Ctr Tianjin Med Epigenet 2011, Tianjin, Peoples R China; 2.Shanghai Jiao Tong Univ, Sch Life Sci & Biotechnol, State Key Lab Med Genom, Shanghai, Peoples R China; 3.Shanghai Jiao Tong Univ, Dept Pediat Cardiol, Sch Med, Xinhua Hosp, Shanghai, Peoples R China; 4.Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA, 5.Chinese Acad Sci, Grad Sch, Shanghai Inst Biol Sci, Key Lab Food Safety Res,Inst Nutr Sci, Shanghai, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Wang, Yuanyang,Chen, Guilin,Liu, Qian,et al. Prostaglandin F-2 Facilitates Hepatic Glucose Production Through CaMKII/p38/FOXO1 Signaling Pathway in Fasting and Obesity[J]. DIABETES,2018,67(9):1748-1760. |
| APA | Wang, Yuanyang.,Chen, Guilin.,Liu, Qian.,Shen, Yujun.,Yu, Ying.,...&,.(2018).Prostaglandin F-2 Facilitates Hepatic Glucose Production Through CaMKII/p38/FOXO1 Signaling Pathway in Fasting and Obesity.DIABETES,67(9),1748-1760. |
| MLA | Wang, Yuanyang,et al."Prostaglandin F-2 Facilitates Hepatic Glucose Production Through CaMKII/p38/FOXO1 Signaling Pathway in Fasting and Obesity".DIABETES 67.9(2018):1748-1760. |
入库方式： OAI收割
来源：上海营养与健康研究所
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