The antiinflammatory cytokine interleukin-1 receptor antagonist protects from high-fat diet-induced hyperglycemia
The antiinflammatory cytokine interleukin-1 receptor antagonist protects from high-fat diet-induced hyperglycemia
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DOI：
10.1210/en.2007-1059
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发表时间：
2008-05-01
期刊：
影响因子：
4.8
通讯作者：
Maedler, Kathrin
中科院分区：
文献类型：
--
作者：
Sauter, Nadine S.;Schulthess, Fabienne T.;Maedler, Kathrin
亚临床炎症是最近在2型糖尿病中发现的一种现象。升高的细胞因子损害β细胞功能和存活。最近的一项临床试验表明，通过IL-1受体拮抗剂（IL-1Ra）阻断IL-1 β信号传导可改善2型糖尿病患者的β细胞分泌功能。在本研究中，我们进一步提供了IL-1Ra对β细胞保护作用的机制。IL-1Ra对高脂高糖饮食（HFD） 12周的C57BL/6J小鼠体内糖尿病有预防作用；它改善了葡萄糖耐量和胰岛素分泌。高脂饮食治疗增加了血清游离脂肪酸和脂肪因子抵抗素和瘦素的水平，而IL-1Ra治疗降低了这些水平。此外，IL-1Ra可抵消脂联素水平，而脂联素水平因高脂喂养而降低。对离体胰岛的研究表明，IL-1Ra特异性作用于β细胞。IL-1Ra保护HFD处理动物的胰岛免于β细胞凋亡，诱导β细胞增殖，并改善葡萄糖刺激的胰岛素分泌。胰岛素mRNA在喂食HFD的小鼠胰岛中减少，但在IL-1Ra组中恢复正常。我们的研究结果表明，IL-1Ra可以改善β细胞的存活和功能，并支持IL-1Ra在糖尿病治疗中的潜在作用。
Subclinical inflammation is a recently discovered phenomenon in type 2 diabetes. Elevated cytokines impair beta-cell function and survival. A recent clinical trial shows that blocking IL-1 beta signaling by IL-1 receptor antagonist (IL-1Ra) improves beta-cell secretory function in patients with type 2 diabetes. In the present study, we provide further mechanisms of the protective role of IL-1Ra on the beta-cell. IL-1Ra prevented diabetes in vivo in C57BL/6J mice fed a high-fat/high-sucrose diet (HFD) for 12 wk; it improved glucose tolerance and insulin secretion. High-fat diet treatment increased serum levels of free fatty acids and of the adipokines resistin and leptin, which were reduced by IL-1Ra treatment. In addition, IL-1Ra counteracted adiponectin levels, which were decreased by high-fat feeding. Studies on isolated islets revealed that IL-1Ra specifically acted on the beta-cell. IL-1Ra protected islets from HFD treated animals from beta-cell apoptosis, induced beta-cell proliferation, and improved glucose-stimulated insulin secretion. Insulin mRNA was reduced in islets from mice fed a HFD but normalized in the IL-1Ra group. Our results show that IL-1Ra improves beta-cell survival and function, and support the potential role for IL-1Ra in the treatment of diabetes.