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| 葡萄糖诱导胰岛素β细胞表达胰腺衍生因子的机制 |
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| Mechanisms of glucose-induced expression of pancreatic-derived factor in pancreatic β-cells |
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| Wang O., Cai K., Pang S., Wang T., Qi D., Zhu Q., Ni Z., Le Y. 2009/5/29 18:38:57 |
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Endocrinology, 2008, Volume 149, Issue 2
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| Pancreatic-derived factor (PANDER) is a cytokine-like peptide highly expressed in pancreatic β-cells. PANDER was reported to promote apoptosis of pancreatic β-cells and secrete in response to glucose. Here we explored the effects of glucose on PANDER expression, and the underlying mechanisms in murine pancreatic β-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-κB inhibitor and nonspecific antioxidant), and N-acetylcysteine (antioxidant) were also found to inhibit glucose-induced PANDER promoter activation and gene expression. Because there is nonuclear factor-κB 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 β-cells through multiple signaling pathways. Because PANDER is expressed by pancreatic β-cells and in response to glucose in a similar way to those of insulin, PANDER may be involved in glucose homeostasis. Copyright © 2008 by The Endocrine Society. |
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| Correspondence Address: Le, Y.; Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 294 Taiyuan Road, Shanghai 200031, China; email: yyle@sibs.ac.cn |
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 疾病资源中心
摘自：《西氏内科学》，第23版
患者女性，21岁，因干咳、间歇性气促2个月到急诊科就诊。开始症状为上呼吸道感染引起的鼻塞、流涕和咳嗽。医生检查后开了抗生素。服药后鼻部症状缓解，但仍有轻微干咳和呼吸困难。其他症状包括疲劳和焦虑。否认发热、体重减轻、胸痛、端坐呼吸、气喘、鼻后滴漏、胃灼热以及神经系统症状。
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