Influence of protease on inhibitory and stimulatory effects of interleukin 1 beta on beta-cell function.
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.
Welsh
N
N
Department of Medical Cell Biology, Uppsala University, Sweden.
Bendtzen
K
K
Sandler
S
S
D000818:Animals; D002469:Cell Separation; D004247:DNA / Q000378:metabolism; D010450:Endopeptidases / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012697:Serine Endopeptidases / Q000502:physiology; D014107:Tosyllysine Chloromethyl Ketone / Q000494:pharmacology
D007328:Insulin; D007375:Interleukin-1; D014107:Tosyllysine Chloromethyl Ketone; D004247:DNA; D010450:Endopeptidases; D012697:Serine Endopeptidases; D005947:Glucose