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Diabetologia:胰腺脂肪和脂肪肝之间的代谢交联:对局部炎症和胰岛素分泌的影响

2018-01-01 MedSci MedSci原创

近日,国际杂志 《Diabetic Med》上在线发表一项关于胰腺脂肪和脂肪肝之间的代谢交联对局部炎症和胰岛素分泌的影响的研究。 肥胖相关的异位脂肪堆积与2型糖尿病的发展有关。关于胰腺和肝脏的脂肪变性是否影响胰岛素分泌仍然是有争议的。在本研究中,研究人员调查了人类胰岛脂肪细胞与胰岛的交叉作用以及致糖尿病因子,即棕榈酸酯和胎球蛋白-A(一种从脂肪肝释放的肝细胞因子)的作用。 研究人员对人

近日,国际杂志 《Diabetologia》上在线发表一项关于胰腺脂肪和脂肪肝之间的代谢交联对局部炎症和胰岛素分泌的影响的研究。

肥胖相关的异位脂肪堆积与2糖尿病的发展有关。关于胰腺和肝脏的脂肪变性是否影响胰岛素分泌仍然是有争议的。在本研究中,研究人员调查了人类胰岛脂肪细胞与胰岛的交叉作用以及致糖尿病因子,即棕榈酸酯和胎球蛋白-A(一种从脂肪肝释放的肝细胞因子)的作用。

研究人员对人类切除胰腺进行胰岛素,胰高血糖素,生长抑素和巨噬细胞/单核细胞标志物CD68进行免疫组织化学染色。通过Oil Red O和脂联素染色鉴定胰脂肪细胞。将原代胰腺前脂肪细胞和分化的脂肪细胞与从器官供体分离的胰岛一起培养,通过添加棕榈酸酯和胎球蛋白A来模拟脂肪肝和脂肪胰腺之间的代谢交联。通过ELISARIA评估胰岛素分泌。通过RT-PCR和多重测定分别评估细胞因子表达和分泌。通过共聚焦显微镜检查蛋白质的亚细胞分布,并通过western印迹检测蛋白质磷酸化。

研究发现,在人类胰腺实质中,在具有正常结构和激素分布的胰岛附近检测到高度分化的脂肪细胞。脂肪细胞浸润与胰岛内CD68阳性细胞数目增加有关。在分离的原代胰腺前脂肪细胞和分化的脂肪细胞中,棕榈酸酯和胎球蛋白A诱导了IL6CXCL8CCL2 mRNA的表达。细胞因子的产生是前脂肪细胞中的toll样受体4TLR4)依赖性的,且当与胰岛共培养时,进一步累积。在胰岛中,加入胎球蛋白A和棕榈酸酯使得IL6CXCL8 mRNA水平增加。只有在分离的胰岛内的巨噬细胞中,棕榈酸酯和胎球蛋白-A刺激细胞毒性细胞因子IL-1β的产生。软脂酸在胰岛细胞中发挥促凋亡作用,而不是胎球蛋白A。相反,胎球蛋白A以不依赖于TLR4但以c-Jun N端激酶和Ca 2+依赖的方式损害葡萄糖诱导的胰岛素分泌。

这些结果提供了关于胎球蛋白A介导的脂肪肝与胰岛的代谢交联可能是导致肥胖相关的β细胞的葡萄糖反应盲区,而胰腺脂肪可能加剧局部炎症的首次证据。

原始出处:

Felicia Gerst, Robert Wagner, Gabriele Kaiser, et al. Metabolic crosstalk between fatty pancreas and fatty liver: effects on local inflammation and insulin secretion

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    2018-02-15 baoya
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    2018-07-18 gwc392
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    2018-01-03 chg122
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    2018-01-01 1e0e5697m83(暂无匿称)

    henhao

    0

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    2018-01-01 131****1460

    学习了受益匪浅

    0

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