Interleukin (IL)-1beta toxicity to islet beta cells: Efaroxan exerts a complete protection

Journal of Cellular Physiology
Gianpaolo PapaccioFerdinando Nicoletti

Abstract

Interleukin (IL)-1beta-treated rat islets of Langerhans were exposed in vitro either to the imidazoline compound, Efaroxan, or to the selective inducible nitric oxide synthase (iNOS) inhibitor, 1400W, in a medium containing a high concentration of glucose (16.7 mmol/L). Our data have evidenced the following: (i) addition of Efaroxan to islet cultures inhibited IL-1beta activation of ICE (cysteine protease IL-1beta converting enzyme) while addition of 1400W did not; (ii) Efaroxan completely inhibited IL-1beta-induced suppression of insulin secretion and induction of iNOS mRNA transcripts, and, in addition, counteracted islet beta-cell protein profile alterations, Bax-cytochrome c translocation, caspase activation, and apoptosis; (iii) 1400W inhibited IL-1beta induction of iNOS, but failed to completely counteract the other cytotoxic effects; (iv) the two compounds, moreover, exerted different effects on manganese superoxide dismutase (MnSOD), in fact, while Efaroxan inhibited the early stimulatory effect of IL-1beta on MnSOD, 1400W did not. Thus, Efaroxan completely protected islet beta cells from damage caused by IL-1beta-induced toxicity, while compound 1400W only inhibited NO radical production without altering the cytokine's...Continue Reading

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Citations

May 28, 2009·Diabetes·Lars G GrunnetThomas Mandrup-Poulsen
Nov 16, 2018·PloS One·Kohei TakedaYuichi Izumi
Apr 1, 2009·Journal of Cellular Physiology·Alice SchwarznauLuis A Fernandez
Feb 12, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Kathrin MaedlerRaphael Roduit

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