Welsh N, Bendtzen K, Sandler S
Department of Medical Cell Biology, Uppsala University, Sweden.
Diabetes. 1991 Feb;40(2):290-4. doi: 10.2337/diab.40.2.290.
To elucidate the putative role of proteases in the action of interleukin 1 beta (IL-1 beta) on pancreatic beta-cells, we studied the effects on islet function of different protease inhibitors when added together with recombinant IL-1 beta to isolated rat pancreatic islets. It was found that the trypsin inhibitor N alpha-p-tosyl-L-lysine chloromethyl ketone (TLCK) counteracted the acute stimulatory effects of IL-1 beta on islet glucose oxidation, insulin release, and biosynthesis. TLCK also partially or completely counteracted the long-term inhibitory effects of IL-1 beta on islet glucose oxidation, insulin biosynthesis, content, and release. This protease inhibitor also counteracted IL-1 beta-induced beta-cell cytotoxicity as assessed by DNA content measurements. Of the other group-specific protease inhibitors investigated, only N-tosyl-L-phenylalanine chloromethyl ketone, N alpha-p-tosyl-L-arginine methyl ester, and chloromercuriphenylsulfonic acid were found to partially protect against IL-1 beta action. We concluded that protease activation, putatively a serine protease, may be an early and perhaps primary event in the action of IL-1 beta on beta-cells.
为阐明蛋白酶在白细胞介素1β（IL-1β）对胰腺β细胞作用中的假定作用，我们研究了将不同蛋白酶抑制剂与重组IL-1β一起添加到分离的大鼠胰岛中时对胰岛功能的影响。发现胰蛋白酶抑制剂Nα-对甲苯磺酰-L-赖氨酸氯甲基酮（TLCK）可抵消IL-1β对胰岛葡萄糖氧化、胰岛素释放和生物合成的急性刺激作用。TLCK还部分或完全抵消了IL-1β对胰岛葡萄糖氧化、胰岛素生物合成、含量和释放的长期抑制作用。通过DNA含量测量评估，这种蛋白酶抑制剂还可抵消IL-1β诱导的β细胞细胞毒性。在所研究的其他组特异性蛋白酶抑制剂中，仅发现N-对甲苯磺酰-L-苯丙氨酸氯甲基酮、Nα-对甲苯磺酰-L-精氨酸甲酯和氯汞苯磺酸可部分保护胰岛免受IL-1β的作用。我们得出结论，蛋白酶激活（可能是一种丝氨酸蛋白酶）可能是IL-1β对β细胞作用中的早期且可能是主要事件。
