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Mechanisms of glucose-induced expression of pancreatic-derived factor in pancreatic beta-cells

文献类型:期刊论文

作者Wang, Oumei1,2; Cai, Kun1,2; Pang, Shanshan1,2; Wang, Ting1,2; Qi, Dongfei1,2; Zhu, Quanfeng1,2; Ni, Zimei1,2; Le, Yingying1,2
刊名Endocrinology
出版日期2008-02-01
卷号149期号:2页码:672-680
ISSN号0013-7227
DOI10.1210/en.2007-0106
通讯作者Le, yingying(yyle@sibs.ac.cn)
英文摘要Pancreatic-derived factor (pander) is a cytokine-like peptide highly expressed in pancreatic beta-cells. pander was reported to promote apoptosis of pancreatic beta-cells and secrete in response to glucose. here we explored the effects of glucose on pander expression, and the underlying mechanisms in murine pancreatic beta-cell line min6 and primary islets. our results showed that glucose up-regulated pander mrna and protein levels in a time-and dose-dependent manner in min6 cells and pancreatic islets. in cells expressing camp response element-binding protein (creb) dominant-negative construct, glucose failed to induce pander gene expression and promoter activation. treatment of the cells with calcium chelator [egta, 1,2-bis(o-aminophenoxy) ethane-n, n, n', n'-tetraacetic acid tetra(acetoxymethyl) ester (bapta/ am)], the voltage-dependent ca2+ channel inhibitor (nifedipine), the protein kinase a (pka) inhibitor (h89), the protein kinase c (pkc) inhibitor (go6976), or the mapk kinase 1/2 inhibitor (pd98059), all significantly inhibited glucose-induced pander gene expression and promoter activation. further studies showed that glucose induced creb phosphorylation through ca2+-pka-erk1/2 and ca2+-pkc pathways. thus, the ca2+-pka-erk1/2-creb and ca2+-pkc-creb signaling pathways are involved in glucose-induced pander gene expression. wortmannin(phosphatidylinositol 3-kinase inhibitor), ammonium pyrrolidinedithiocarbamate (nuclear factor-kappa b inhibitor and nonspecific antioxidant), and n-acetylcysteine (antioxidant) were also found to inhibit glucose-induced pander promoter activation and gene expression. because there is no nuclear factor-kappa b binding site in the promoter region of pander gene, these results suggest that phosphatidylinositol 3-kinase and reactive oxygen species be involved in glucose-induced pander gene expression. in conclusion, glucose induces pander gene expression in pancreatic beta-cells through multiple signaling pathways. because pander is expressed by pancreatic beta-cells and in response to glucose in a similar way to those of insulin, pander may be involved in glucose homeostasis.
WOS关键词INSULIN GENE-TRANSCRIPTION ; GROWTH RESPONSE-1 GENE ; KAPPA-B ACTIVATION ; ENDOTHELIAL-CELLS ; PROMOTER ACTIVITY ; FACTOR PANDER ; FACTOR FAM3B ; PROTEIN ; PHOSPHORYLATION ; PATHWAY
WOS研究方向Endocrinology & Metabolism
WOS类目Endocrinology & Metabolism
语种英语
WOS记录号WOS:000252506800030
出版者ENDOCRINE SOC
URI标识http://www.irgrid.ac.cn/handle/1471x/2386317
专题中国科学院大学
通讯作者Le, Yingying
作者单位1.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Shanghai 200031, Peoples R China
2.Chinese Acad Sci, Grad Sch, Shanghai 200031, Peoples R China
推荐引用方式
GB/T 7714
Wang, Oumei,Cai, Kun,Pang, Shanshan,et al. Mechanisms of glucose-induced expression of pancreatic-derived factor in pancreatic beta-cells[J]. Endocrinology,2008,149(2):672-680.
APA Wang, Oumei.,Cai, Kun.,Pang, Shanshan.,Wang, Ting.,Qi, Dongfei.,...&Le, Yingying.(2008).Mechanisms of glucose-induced expression of pancreatic-derived factor in pancreatic beta-cells.Endocrinology,149(2),672-680.
MLA Wang, Oumei,et al."Mechanisms of glucose-induced expression of pancreatic-derived factor in pancreatic beta-cells".Endocrinology 149.2(2008):672-680.

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