To elucidate the putative role of proteases in the action of interleukin 1 p (IL-1 p) on pancreatic p-cells, we studied the effects on islet function of different protease inhibitors when added together with recombinant IL-1 p to isolated rat pancreatic islets. It was found that the trypsin inhibitor A/a-p-tosyl-L-lysine chloromethyl ketone (TLCK) counteracted the acute stimulatory effects of IL-1 p on islet glucose oxidation, insulin release, and biosynthesis. TLCK also partially or completely

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... counteracted the long-term inhibitory effects of IL-1 p on islet glucose oxidation, insulin biosynthesis, content, and release. This protease inhibitor also counteracted IL-1 p-induced p-cell cytotoxicity as assessed by DNA content measurements. Of the other group-specific protease inhibitors investigated, only AMosyl-L-phenylalanine chloromethyl ketone, A/a-p-tosyl-L-arginine methyl ester, and chloromercuriphenylsulfonic acid were found to partially protect against IL-1 p action. We concluded that protease activation, putatively a serine protease, may be an early and perhaps primary event in the action of IL-1 p on p-cells. Diabetes