Faculty Collaboration Database

Tyrosine kinase involvement in IL-1 beta-induced expression of iNOS by beta-cells purified from islets of Langerhans. Am J Physiol 1994 Jul;267(1 Pt 1):C48-54

Date

07/01/1994

Pubmed ID

7519400

DOI

10.1152/ajpcell.1994.267.1.C48

Scopus ID

2-s2.0-0028112591 (requires institutional sign-in at Scopus site)   81 Citations

Abstract

Nitric oxide is believed to mediate the inhibitory effects of cytokines on glucose-stimulated insulin secretion by both rat and human islets. The aims of this study were 1) to determine the cellular source of the cytokine-inducible isoform of nitric oxide synthase (iNOS) expressed in islets following cytokine stimulation and 2) to determine whether tyrosine kinase activity participates in cytokine-induced iNOS expression. In this report we demonstrate that the cytokine interleukin-1 beta (IL-1 beta) stimulates the expression of iNOS and the formation of nitric oxide (as determined by nitrite formation, a stable oxidative product of nitric oxide) by isolated intact rat islets and by primary beta-cells purified by fluorescence-activated cell sorting (FACS). Both the expression of iNOS and nitrite formation induced by IL-1 beta were prevented by the mRNA transcriptional inhibitor actinomycin D. IL-1 beta did not induce the expression of iNOS by FACS-purified alpha-cells, the other major endocrine cell type of the islet. The tyrosine kinase inhibitors genistein and herbimycin A prevented IL-1 beta-induced expression of immunoprecipitable iNOS and nitrite release by islets, by insulinoma RINm5F cells, and by FACS-purified beta-cells. Herbimycin A and genistein also prevented IL-1 beta-induced iNOS mRNA accumulation as determined by Northern blot analysis of total RNA isolated from RINm5F cells. These findings indicate tyrosine kinase activation participates in IL-1 beta-induced expression of iNOS by the insulin-secreting beta-cell.(ABSTRACT TRUNCATED AT 250 WORDS)

Author List

Corbett JA, Kwon G, Misko TP, Rodi CP, McDaniel ML

Author

John A. Corbett PhD Chair, Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amino Acid Oxidoreductases
Animals
Enzyme Induction
Interleukin-1
Islets of Langerhans
Isoenzymes
Male
Nitric Oxide Synthase
Precipitin Tests
Protein-Tyrosine Kinases
RNA, Messenger
Rats
Rats, Sprague-Dawley