Liposomal delivery of antioxidant enzymes protects against hydrogen peroxide- but not interleukin-1 beta-induced inhibition of glucose metabolism in rat pancreatic islets.
The aim of the present investigation was to evaluate the putative involvement of oxygen free radicals in interleukin-1 beta (IL-1 beta)-induced suppression of islet glucose oxidation. Isolated adult rat pancreatic islets were exposed for 1 h to liposomally encapsulated superoxide dismutase (SOD; 10 mg/ml), catalase (CAT; 10 mg/ml) and glutathione peroxidase (GPX; 5 mg/ml), after which IL-1 beta (25 U/ml) or hydrogen peroxide (H2O2; 0.1 mM) was added, and the incubation was continued overnight. The following day, samples were taken from the incubation media for nitrite determinations, and islet glucose oxidation rates were measured. The CAT activity increased fourfold after addition of CAT-containing liposomes. It was found that IL-1 beta induced a marked increase in islet nitrite production, as an index of nitric oxide formation, and that this was paralleled by a decrease in islet glucose oxidation rates. H2O2-treated islets exhibited a modest decrease in glucose oxidation rates and a minor increase in the release of nitrite to the media. Treatment of islets with liposomes containing the antioxidant enzymes SOD, CAT and GPX, either alone or in combination, did not decrease the effect of IL-1 beta. However, the H2O2-induced decrease in glucose oxidation rates was counteracted by the combination of the antioxidants. It was concluded that, provided the intracellular delivery of the antioxidant enzymes to the islet cells was effective, oxygen free radicals probably do not play a decisive role in IL-1 beta suppression of islet glucose metabolism.
Department of Medical Cell Biology, Uppsala University, Sweden.
N
N
Welsh
B
B
Margulis
K
K
Bendtzen
S
S
Sandler
D000818:Animals; D002374:Catalase / Q000494:pharmacology; D002478:Cells, Cultured; D004337:Drug Carriers; D005947:Glucose / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008081:Liposomes; D008297:Male; D009573:Nitrites / Q000378:metabolism; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000494:pharmacology
D004337:Drug Carriers; D007375:Interleukin-1; D008081:Liposomes; D009573:Nitrites; D006861:Hydrogen Peroxide; D010088:Oxidoreductases; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005947:Glucose