Interleukin 1 inhibits insulin secretion from isolated rat pancreatic islets by a process that requires gene transcription and mRNA translation.
Interleukin 1 inhibits insulin secretion from isolated rat pancreatic islets by a process that requires gene transcription and mRNA translation.
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白细胞介素 1 通过需要基因转录和 mRNA 翻译的过程抑制离体大鼠胰岛的胰岛素分泌。
DOI：
10.1172/jci114785
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
McDaniel,ML
中科院分区：
文献类型：
--
作者：
Hughes,JH;Colca,JR;Easom,RA;Turk,J;McDaniel,ML
重组人IL 1 β抑制来自分离的胰岛和来自通过分散的胰岛细胞的荧光激活细胞分选（FACS）获得的纯化的β细胞的葡萄糖诱导的胰岛素分泌。分离的胰岛短暂（1小时）暴露于IL 1产生持续的胰岛素分泌抑制至少17小时后，IL 1已从培养基中删除。当胰岛与DNA转录抑制剂（放线菌素D）共孵育时，未观察到IL 1对胰岛素分泌的抑制作用。这一发现表明，IL 1对胰岛素分泌的抑制作用需要在胰岛暴露于IL 1的第一个小时期间转录一个或多个基因。IL 1对胰岛素分泌的抑制作用也需要mRNA翻译，因为当在IL 1暴露1小时后加入胰岛时，三种结构不同的蛋白质合成抑制剂（放线菌酮、茴香霉素和嘌呤霉素）阻止IL 1诱导的胰岛素分泌抑制。用[35 S]蛋氨酸代谢标记的胰岛蛋白质的二维凝胶电泳表明，IL 1使65 kD（pI约6.5）蛋白质的表达增加2.5倍以上。这些发现表明，胰岛暴露于IL 1后1小时内发生的生化事件导致胰岛素分泌抑制，在去除IL 1后至少持续17小时。IL 1对胰岛的早期生化作用之一是基因转录（0-1小时），随后是mRNA翻译（1小时后）。我们的研究结果表明IL 1对胰岛素分泌的抑制作用是由IL 1诱导合成的蛋白介导的。图片
Recombinant human IL 1 beta inhibits glucose-induced insulin secretion from isolated pancreatic islets and from purified beta-cells obtained by fluorescence-activated cell sorting (FACS) of dispersed islet cells. Brief (1 h) exposure of isolated islets to IL 1 produces sustained inhibition of insulin secretion for at least 17 h after the IL 1 has been removed from the culture medium. An inhibitory effect of IL 1 on insulin secretion is not observed when islets are coincubated with an inhibitor of DNA transcription (actinomycin D). This finding indicates that the inhibitory effect of IL 1 on insulin secretion requires transcription of one or more genes during the first hour of exposure of islets to IL 1. The inhibitory effect of IL 1 on insulin secretion also requires mRNA translation, because three structurally distinct inhibitors of protein synthesis (cycloheximide, anisomycin, and puromycin) prevent IL 1-induced inhibition of insulin secretion when added to islets after the 1-h exposure to IL 1. Two-dimensional gel electrophoresis of islet proteins metabolically labeled with [35S]methionine demonstrates that IL 1 augments the expression of a 65-kD (pl approximately 6.5) protein by greater than 2.5-fold. These findings indicate that biochemical events occurring within 1 h of exposure of islets to IL 1 lead to an inhibition of insulin secretion that persists for at least 17 h after the removal of IL 1. One of the early biochemical effects of IL 1 on islets is gene transcription (0-1 h), which is followed by mRNA translation (after 1 h). Our results suggest that the inhibitory effect of IL 1 on insulin secretion is mediated by protein(s) whose synthesis is induced by IL 1.Images