Interleukin-6 enhances glucose-stimulated insulin secretion from pancreatic beta-cells: potential involvement of the PLC-IP3-dependent pathway.
Interleukin-6 enhances glucose-stimulated insulin secretion from pancreatic beta-cells: potential involvement of the PLC-IP3-dependent pathway.
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DOI：
10.2337/db10-0796
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发表时间：
2011-02
期刊：
影响因子：
7.7
通讯作者：
Katagiri H
中科院分区：
文献类型：
--
作者：
Suzuki T;Imai J;Yamada T;Ishigaki Y;Kaneko K;Uno K;Hasegawa Y;Ishihara H;Oka Y;Katagiri H
白细胞介素-6 （IL-6）对葡萄糖代谢有显著影响。然而，IL-6对胰腺β细胞分泌胰岛素的影响尚存争议。因此，我们在体内和体外分析了IL-6对胰腺β细胞功能的影响。首先，为了研究IL-6对体内胰岛素分泌的影响，我们使用腺病毒基因转移系统在小鼠肝脏中表达IL-6。此外，我们利用小鼠β细胞系MIN-6细胞和小鼠胰岛，分析了IL-6预处理对胰岛素分泌的体外影响。此外，利用药物抑制剂和小干扰rna，我们研究了IL-6可能影响MIN-6细胞胰岛素分泌的细胞内信号通路。肝脏IL-6的表达提高了循环IL-6和葡萄糖耐量，这是由于葡萄糖刺激胰岛素分泌（GSIS）的增强。此外，在离体胰岛和MIN-6细胞中，IL-6预处理24小时可显著增强GSIS。此外，用不同作用机制的磷脂酶C （PLC）抑制剂U-73122和新霉素预处理MIN-6细胞，并敲低IL-6受体和PLC-β1，而不使用蛋白激酶a抑制剂H-89，可以抑制IL-6诱导的GSIS增强。肌醇三磷酸（IP3）受体拮抗剂Xestospondin C也能消除IL-6诱导的GSIS增强。体内和体外实验结果强烈提示IL-6直接作用于胰腺β细胞，增强GSIS。plc - ip3依赖性通路可能参与il -6介导的GSIS增强。
Interleukin-6 (IL-6) has a significant impact on glucose metabolism. However, the effects of IL-6 on insulin secretion from pancreatic β-cells are controversial. Therefore, we analyzed IL-6 effects on pancreatic β-cell functions both in vivo and in vitro. First, to examine the effects of IL-6 on in vivo insulin secretion, we expressed IL-6 in the livers of mice using the adenoviral gene transfer system. In addition, using both MIN-6 cells, a murine β-cell line, and pancreatic islets isolated from mice, we analyzed the in vitro effects of IL-6 pretreatment on insulin secretion. Furthermore, using pharmacological inhibitors and small interfering RNAs, we studied the intracellular signaling pathway through which IL-6 may affect insulin secretion from MIN-6 cells. Hepatic IL-6 expression raised circulating IL-6 and improved glucose tolerance due to enhancement of glucose stimulated-insulin secretion (GSIS). In addition, in both isolated pancreatic islets and MIN-6 cells, 24-h pretreatment with IL-6 significantly enhanced GSIS. Furthermore, pretreatment of MIN-6 cells with phospholipase C (PLC) inhibitors with different mechanisms of action, U-73122 and neomycin, and knockdowns of the IL-6 receptor and PLC-β1, but not with a protein kinase A inhibitor, H-89, inhibited IL-6–induced enhancement of GSIS. An inositol triphosphate (IP3) receptor antagonist, Xestospondin C, also abrogated the GSIS enhancement induced by IL-6. The results obtained from both in vivo and in vitro experiments strongly suggest that IL-6 acts directly on pancreatic β-cells and enhances GSIS. The PLC-IP3–dependent pathway is likely to be involved in IL-6-mediated enhancements of GSIS.