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| 过氧化酶增殖体活化受体调节大鼠胰岛细胞瘤细胞（INS-1）胰十二指肠同源盒-1表达并可以改善棕榈酸盐损伤的葡萄糖诱导的胰岛素分泌 |
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| Peroxisome proliferator-activated receptor-α regulates the expression of pancreatic/duodenal homeobox-1 in rat insulinoma (INS-1) cells and ameliorates glucose-induced insulin secretion impaired by palmitate |
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| Sun Y., Zhang L., Gu H.F., Han W., Ren M., Wang F., Gong B., Wang L., Guo H., Xin W., Zhao J., Gao L. 2009/5/29 18:38:57 |
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Endocrinology, 2008, Volume 149, Issue 2
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| Both peroxisome proliferator-activated receptor-α (PPARα) and pancreatic/duodenal homeobox-1 (PDX-1) have been reported to be associated with glucose-stimulated insulin secretion (GSIS), but the relationship between PPARα and PDX-1 is not yet fully understood. In the present study, we tested the hypothesis that PPARα regulates the expression of PDX-1 in β-cells. Isolated pancreatic islets from Wistar rats and rat pancreatic insulinoma (INS-1) β-cells were cultured in media supplemented with and without 0.2 or 0.4 mM palmitate, and treated with and without a PPARα agonist (fenofibrate) or PPARα antagonist (MK886). Results indicated that treatment with fenofibrate significantly enhanced PPARα mRNA and protein expression in cells cultured with elevated palmitate concentrations compared with cells that did not receive fenofibrate treatment. In turn, this enhanced expression led to an increase in PDX-1 mRNA and nuclear protein, as well as DNA binding activity of PDX-1 with the insulin promoter. Accordingly, the expression of the PDX-1 downstream targets, insulin and glucose transporter-2, increased, resulting in increased intracellular insulin content and GSIS. Treatment with MK886 inhibited expression of PPARα, blocking PPARα-regulated PDX-1 expression, and the downstream transcription events of PDX-1. EMSA revealed that nuclear protein might bind with the peroxisome proliferator response element sequence located in the PDX-1 promoter. Collectively, these results demonstrate a regulatory relationship between PPARα and PDX-1 in INS-1 cells. Furthermore, PPARα activation potentiates GSIS under elevated palmitate conditions possibly via up-regulation of PDX-1. Our findings have potential clinical implications for the use of PPARα agonists in the treatment of type 2 diabetes. Copyright © 2008 by The Endocrine Society. |
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| Correspondence Address: Zhao, J.; Department of Endocrinology, Shandong Provincial Hospital, Shandong University, 324 Jing 5 Road, Jinan, Shandong Province, 250021, China; email: jjzhao@medmail.comcn |
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 疾病资源中心
王燕燕 王曙
上海交通大学附属瑞金医院内分泌科
患者，女，69岁。2009年1月无明显诱因下出现乏力，当时程度较轻，未予以重视。2009年3月患者乏力症状加重，尿色逐渐加深，大便习惯改变，颜色变淡。4月18日入我院感染科治疗，诉轻度头晕、心慌，体重减轻10kg。无肝区疼痛，无发热，无腹痛、腹泻、腹胀、里急后重，无恶性、呕吐等。入院半月前于外院就诊，查肝功能：ALT 601IU/L，AST 785IU/L，TBIL 97.7umol/L，白蛋白 41g/L，甲状腺功能：游离T3 30.6pmol/L，游离T4 51.9pmol/L，心电图示快速房颤。
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