Interleukin-1 beta-induced formation of EPR-detectable iron-nitrosyl complexes in islets of Langerhans. Role of nitric oxide in interleukin-1 beta-induced inhibition of insulin secretion. J Biol Chem 1991 Nov 15;266(32):21351-4
Date
11/25/1991Pubmed ID
1657959Scopus ID
2-s2.0-0025720502 (requires institutional sign-in at Scopus site) 279 CitationsAbstract
The molecular mechanism by which interleukin (IL)-1 inhibits insulin secretion and ultimately causes destruction of the pancreatic beta-cell remains unknown. Evidence is presented which suggests that IL-1 beta-induced inhibition of insulin secretion is dependent on the metabolism of L-arginine to nitric oxide. NG-Monomethylarginine, a competitive inhibitor of the L-arginine-dependent enzyme nitric oxide synthase, completely prevents IL-1-induced inhibition of glucose-stimulated insulin secretion as well as nitrite production by islets. It is further shown that IL-1 beta induces nitric oxide formation in islets as evidenced by an electron paramagnetic resonance feature at g = 2.04 which is similar to previously reported iron-nitrosyl complexes formed from the destruction of iron-sulfur centers by nitric oxide. Inhibition of the nitric oxide synthase by NG-monomethylarginine completely prevents the formation of this EPR signal in islets. These results show that IL-1-induced inhibition of insulin secretion is mediated through formation of nitric oxide and suggest that the generation of nitric oxide may represent the cellular mechanism responsible for beta-cell destruction.
Author List
Corbett JA, Lancaster JR Jr, Sweetland MA, McDaniel MLAuthor
John A. Corbett PhD Chair, Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsArginine
Cells, Cultured
Electron Spin Resonance Spectroscopy
Interleukin-1
Iron-Sulfur Proteins
Islets of Langerhans
Kinetics
Male
Nitric Oxide
Nitrites
Rats
Rats, Inbred Strains
Recombinant Proteins
omega-N-Methylarginine
