A stress response pathway in mice upregulates somatostatin level and transcription in pancreatic delta cells through Gs and beta-arrestin 1

doi:10.1007/s00125-014-3290-0

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	A stress response pathway in mice upregulates somatostatin level and transcription in pancreatic delta cells through Gs and beta-arrestin 1
	Wang, Hong-Mei 1; Dong, Jun-Hong 1,2,3; Li, Qing 1; Hu, Qiaoxia 2,4; Ning, Shang-Lei 5; Zheng, Wenshuai 1; Cui, Min 1; Chen, Tian-Sheng 6; Xie, Xin7 ; Sun, Jin-Peng 2,4
刊名	DIABETOLOGIA
	2014-09
卷号	57 期号:9 页码:1899-1910
关键词	Adrenergic receptors beta-Arrestin 1 CREB Pancreatic delta cell PAX6 PDX1 Somatostatin Stress
ISSN号	0012-186X
DOI	10.1007/s00125-014-3290-0
文献子类	Article
英文摘要	Aims/hypothesis Somatostatin secretion from islet delta cells plays an important role in regulating islet function and is tightly controlled by environmental changes. Activation of the adrenergic system promoted somatostatin secretion from islet delta cells; however, the role of the adrenergic system in regulating somatostatin content and transcription has not been defined. An imbalance between the somatostatin content and its secretion may cause dysfunctions in the islet delta cells. We have investigated the role of the adrenergic system in the modulation of somatostatin content and transcription in pancreatic delta cells and the detailed underlying mechanisms of this regulation. Methods The stress hormone adrenaline (epinephrine), specific adrenergic agonists or specific adrenergic antagonists were applied to islets from either wild-type or specific adrenergic receptor knockout mice and pancreatic delta cell lines to investigate their effects on somatostatin content and transcription. The GloSensor assay, quantitative real-time PCR, western blots and the dual luciferase assay were used to monitor the cAMP level, somatostatin expression, activations of kinases and transcriptional factors. Arrb1 knockout mice, specific Creb or Pax6 mutations and specific kinase inhibitors were used to dissect the signalling pathway. Results Adrenaline and isoprenaline increased somatostatin content and transcription through the activation of beta 1-/beta 2-adrenergic receptors (beta 1-/beta 2ARs). The somatostatin content in beta 1AR(-/-)/beta 2AR(-/-) (Adrb1/Adrb2 knockout) mice was 50% lower than in beta 1AR(+/+)/beta 2AR(+/+) mice. Two parallel signalling pathways, Gs-cAMP-protein kinase A (PKA)-cAMP response element binding protein (CREB) and beta-arrestin 1-extracellular signal-related kinase (ERK)-paired box protein 6 (PAX6), cooperatively regulated isoprenaline-induced somatostatin transcription. Conclusions/interpretation A stress pathway increased somatostatin content and transcription through beta-adrenergic agonism. beta-Arrestin1, ERK and PAX6 are important pancreatic delta cell regulators in addition to cAMP, PKA and CREB. Dysfunction of beta-adrenergic agonism may impair pancreatic delta cell function.
资助项目	National Key Basic Research Program of China[2013CB967700] ; National Key Basic Research Program of China[2012CB910402] ; National Natural Science Foundation of China[31270857] ; National Natural Science Foundation of China[31100580] ; National Natural Science Foundation of China[31271505] ; National Natural Science Foundation of China[81100455] ; Shandong Natural Science Fund for Distinguished Young Scholars[JQ201320] ; Fundamental Research Funds of Shandong University[2014JC029] ; Fundamental Research Funds of Shandong University[2012TS114] ; Program for Changjiang Scholars and Innovative Research Team in University[IRT13028]
WOS关键词	GENE UPSTREAM ENHANCER ; ADRENERGIC-RECEPTOR ; 7-TRANSMEMBRANE RECEPTORS ; INSULIN-SECRETION ; PROTEIN COMPLEX ; PHOSPHORYLATION ; PAX6 ; ACTIVATION ; CREB ; RELEASE
WOS研究方向	Endocrinology & Metabolism
语种	英语
出版者	SPRINGER
WOS记录号	WOS:000340050800021
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276932]
专题	国家新药筛选中心
通讯作者	Yu, Xiao
作者单位	1.Shandong Univ, Sch Med, Dept Physiol, Key Lab Expt Teratol,Minist Educ, Jinan 250012, Shandong, Peoples R China; 2.Shandong Univ, Sch Med, Dept Mol Biol & Biochem, Jinan 250012, Shandong, Peoples R China; 3.Weifang Med Univ, Weifang, Shandong, Peoples R China; 4.Shandong Univ, Key Lab Prot Sci Chron Degenerat Dis, Shandong 250012, Peoples R China; 5.Shandong Univ, Qilu Hosp, Jinan, Shandong, Peoples R China; 6.Huazhong Agr Univ, Coll Fisheries, Key Lab Freshwater Anim Breeding, Wuhan, Hunan, Peoples R China; 7.Shanghai Inst Mat Med, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Wang, Hong-Mei,Dong, Jun-Hong,Li, Qing,et al. A stress response pathway in mice upregulates somatostatin level and transcription in pancreatic delta cells through Gs and beta-arrestin 1[J]. DIABETOLOGIA,2014,57(9):1899-1910.
APA	Wang, Hong-Mei.,Dong, Jun-Hong.,Li, Qing.,Hu, Qiaoxia.,Ning, Shang-Lei.,...&Yu, Xiao.(2014).A stress response pathway in mice upregulates somatostatin level and transcription in pancreatic delta cells through Gs and beta-arrestin 1.DIABETOLOGIA,57(9),1899-1910.
MLA	Wang, Hong-Mei,et al."A stress response pathway in mice upregulates somatostatin level and transcription in pancreatic delta cells through Gs and beta-arrestin 1".DIABETOLOGIA 57.9(2014):1899-1910.