I Prostanoid Receptor-Mediated Inflammatory Pathway Promotes Hepatic Gluconeogenesis Through Activation of PKA and Inhibition of AKT

doi:10.2337/db13-1893

	I Prostanoid Receptor-Mediated Inflammatory Pathway Promotes Hepatic Gluconeogenesis Through Activation of PKA and Inhibition of AKT
	Yan, Shuai ; Zhang, Qianqian ; Zhong, Xiaojing ; Tang, Juan ; Wang, Yuanyang ; Yu, Junjie ; Zhou, Yi ; Zhang, Jian ; Guo, Feifan ; Liu, Yi ; FitzGerald, Garret A.; Yu, Ying
	2014
发表期刊	DIABETES
ISSN	0012-1797
EISSN	1939-327X
卷号	63 期号:9 页码:2911-2923
发表状态	已发表
DOI	10.2337/db13-1893
摘要	Nonsteroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid (ASA), improve glucose metabolism in diabetic subjects, although the underlying mechanisms remain unclear. In this study, we observed dysregulated expression of cyclooxygenase-2, prostacyclin biosynthesis, and the I prostanoid receptor (IP) in the liver's response to diabetic stresses. High doses of ASA reduced hepatic prostaglandin generation and suppressed hepatic gluconeogenesis in mice during fasting, and the hypoglycemic effect of ASA could be restored by IP agonist treatment. IP deficiency inhibited starvation-induced hepatic gluconeogenesis, thus inhibiting the progression of diabetes, whereas hepatic overexpression of IP increased gluconeogenesis. IP deletion depressed cAMP-dependent CREB phosphorylation and elevated AKT phosphorylation by suppressing PI3K-/PKC--mediated TRB3 expression, which subsequently downregulated the gluconeogenic genes for glucose-6-phosphatase (G6Pase) and phosphoenol pyruvate carboxykinase 1 in hepatocytes. We therefore conclude that suppression of IP modulation of hepatic gluconeogenesis through the PKA/CREB and PI3K-/PKC-/TRB3/AKT pathways contributes to the effects of NSAIDs in diabetes.
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WOS研究方向	Endocrinology & Metabolism
WOS类目	Endocrinology & Metabolism
WOS记录号	WOS:000341505300010
WOS关键词	TRANSCRIPTION FACTOR FOXO1 ; GLUCOSE-METABOLISM ; INSULIN SENSITIVITY ; BERAPROST SODIUM ; MICE LACKING ; CELLS ; LIVER ; PROSTACYCLIN ; PROTEIN ; RESISTANCE
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/120763
专题	个人在本单位外知识产出
通讯作者	Yu, Ying
作者单位	1.Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Food Safety Res, Inst Nutr Sci,Grad Sch, Shanghai, Peoples R China 2.Univ Penn, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA 3.Minist Hlth, Key Lab Food Safety Risk Assessment, Beijing, Peoples R China
推荐引用方式 GB/T 7714	Yan, Shuai,Zhang, Qianqian,Zhong, Xiaojing,et al. I Prostanoid Receptor-Mediated Inflammatory Pathway Promotes Hepatic Gluconeogenesis Through Activation of PKA and Inhibition of AKT[J]. DIABETES,2014,63(9):2911-2923.
APA	Yan, Shuai.,Zhang, Qianqian.,Zhong, Xiaojing.,Tang, Juan.,Wang, Yuanyang.,...&Yu, Ying.(2014).I Prostanoid Receptor-Mediated Inflammatory Pathway Promotes Hepatic Gluconeogenesis Through Activation of PKA and Inhibition of AKT.DIABETES,63(9),2911-2923.
MLA	Yan, Shuai,et al."I Prostanoid Receptor-Mediated Inflammatory Pathway Promotes Hepatic Gluconeogenesis Through Activation of PKA and Inhibition of AKT".DIABETES 63.9(2014):2911-2923.