Stickings, P. and Cunningham, J.M. (2002) Interleukin 1β- induced nitric oxide production and inhibition of insulin secretion in rat islets of Langerhans is dependent upon the nitric oxide synthase cofactor tetrahydrobiopterin Cytokine, 18 (2). pp. 81-85. ISSN 1096-0023Full text not available from this repository.
Interleukin (IL)-1β-induced inhibition of glucose-stimulated insulin secretion in rat islets of Langerhans is mediated in part by nitric oxide (NO). The NO synthase cofactor 5,6,7,8-tetrahydrobiopterin (BH4) supports NO synthesis in many cell types and IL-1β-induced NO generation and inhibition of insulin secretion have been previously correlated with intracellular BH4 levels in rat insulinoma cells. Using rat islets and the beta cell line BRIN-BD11, we have investigated whether synthesis of BH4 limits IL-1β-induced NO generation and inhibition of glucose-induced insulin secretion. IL-1β-induced NO generation by BRIN cells and islets was reduced by 2,4-diamino-6-hydroxypyrimidine (DAHP), an inhibitor of de novo BH4 synthesis. Sepiapterin, the substrate for salvage pathway BH4 synthesis, reversed this inhibitory effect of DAHP in islets but not BRIN cells. DAHP reversed IL-1β-induced inhibition of islet insulin secretion, an effect prevented by sepiapterin. We conclude that BH4 generation is necessary for IL-1β-induced NO generation in rat islets and BRIN cells. While a contribution of non-NO mediators cannot be excluded, our results support the proposal that IL-1β-induced, NO-mediated inhibition of insulin secretion in rat islets is dependent on the NOS cofactor BH4.
|Item Type:||Journal article|
|Uncontrolled Keywords:||insulin secretion/interleukin-1β/islets of Langerhans/nitric oxide/tetrahydrobiopterin|
|Subjects:||B000 Health Professions > B200 Pharmacology Toxicology and Pharmacy
A000 Medicine > A300 Clinical Medicine
|DOI (a stable link to the resource):||10.1006/cyto.2002.0881|
|Faculties:||Faculty of Science and Engineering > School of Pharmacy and Biomolecular Sciences|
|Depositing User:||editor spbs|
|Date Deposited:||08 Nov 2007|
|Last Modified:||05 Jun 2013 14:52|
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