Arginase expression and modulation of IL-1β-induced nitric oxide generation in rat and human islets of Langerhans

Stickings, P., Mistry, S.K., Boucher, J.-L., Morris, S.M. and Cunningham, James (2002) Arginase expression and modulation of IL-1β-induced nitric oxide generation in rat and human islets of Langerhans Nitric Oxide: Biology and Chemistry, 7 (4). pp. 289-296. ISSN 1089-8603

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Proinflammatory cytokine induction of NO synthesis may contribute to the destruction of pancreatic beta cells leading to type 1 diabetes. The NO synthase substrate arginine can also be metabolized to ornithine and urea in a reaction catalyzed by cytosolic (AI) or mitochondrial (AII) isoforms of arginase. Recent evidence suggests that the rate of NO generation is dependent on the relative activities of NO synthase and arginase. The objectives of this study were (i) to identify the arginase isoforms expressed in rat and human islets of Langerhans and a rat beta cell line, RINm5F and (ii) to investigate the competition for arginine between NO synthase and arginase in IL-1β-treated rat islets. Arginase activity was detected in rat islets (fresh tissue, 346 mU/mg protein; cultured, 587 mU/mg), cultured human islets (56 mU/mg), RINm5F cells (376 mU/mg), rat kidney (238 mU/mg), and rat liver (6119 mU/mg). Using Western blots, AI was shown to be the predominant isoform expressed in rat islets and in RINm5F cells while human islets expressed far more AII than AI. Rat islets were cultured in medium containing 1.14, 0.1, and 0.01 mM arginine and treated with IL-1β and the arginase inhibitor 2(S)-amino-6-boronohexanoic acid (ABH). IL-1β-induced NO generation was unaffected by ABH at 1.14 mM arginine, but significantly increased at 0.1 and 0.01 mM arginine. These findings suggest that the level of islet arginase activity can regulate the rate of induced NO generation and this may be relevant to the insulitis process leading to beta cell destruction in type 1 diabetes.

Item Type: Journal article
Uncontrolled Keywords: Type 1 diabetes; Nitric oxide synthase; Arginase; Islets of Langerhans; RINm5F; 2(S)-amino-6-boronohexanoic acid
Subjects: A000 Medicine > A300 Clinical Medicine
DOI (a stable link to the resource): 10.1016/S1089-8603(02)00122-2
Faculties: Faculty of Science and Engineering > School of Pharmacy and Biomolecular Sciences
Depositing User: editor spbs
Date Deposited: 27 Nov 2006
Last Modified: 16 Mar 2015 16:02

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