Influence of Protease on Inhibitory and Stimulatory Effects of Interleukin 1β on β-Cell Function

  1. Stellan Sandler
  1. Department of Medical Cell Biology, Uppsala University Uppsala Sweden; and the Laboratory of Medical Immunology, University Hospital Copenhagen, Denmark
  1. Address correspondence and reprint requests to Dr. Nils Welsh, Department of Medical Cell Biology, Biomedicum, PO Box 571, S-751 23 Uppsala, Sweden.

Abstract

To elucidate the putative role of proteases in the action of interleukin 1β (IL-1β) on pancreatic β-cells, we studied the effects on islet function of different protease inhibitors when added together with recombinant IL-1β to isolated rat pancreatic islets. It was found that the trypsin inhibitor Nα-p-tosyl-L-lysine chloromethyl ketone (TLCK) counteracted the acute stimulatory effects of IL-1β on islet glucose oxidation, insulin release, and biosynthesis. TLCK also partially or completely counteracted the long-term inhibitory effects of IL-1β on islet glucose oxidation, insulin biosynthesis, content, and release. This protease inhibitor also counteracted IL-1β–induced β-cell cytotoxicity as assessed by DNA content measurements. Of the other group-specific protease inhibitors investigated, only N-tosyl-L-phenylalanine chloromethyl ketone, Nα-p-tosyl-L-arginine methyl ester, and chloromercuriphenylsulfonic acid were found to partially protect against IL-1 β action. We concluded that protease activation, putatively a serine protease, may be an early and perhaps primary event in the action of IL-1β on β-cells.

  • Received August 31, 1990.
  • Revision received October 17, 1990.
  • Accepted October 17, 1990.
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