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INTERLEUKIN 1βINCREASES ARGININE ACCUMULATION AND ACTIVATES THE CITRULLINE–NO CYCLE IN RAT PANCREATICβCELLS
- Source :
- Cytokine. 11:400-407
- Publication Year :
- 1999
- Publisher :
- Elsevier BV, 1999.
-
Abstract
- Nitric oxide (NO) may contribute to pancreatic beta cell damage during the development of type 1 diabetes. Its formation can be triggered by cytokines which induce the expression of the inducible form of nitric oxide synthase (iNOS) in pancreatic islets. In the iNOS-catalyzed reaction, arginine is converted into citrulline and NO. Cellular NO formation may be regulated by the availability of arginine. Arginine can be provided extracellularly, entering the cell mainly through the cationic amino acid transporter system y+CAT, and intracellularly, by protein degradation or synthesis from citrulline (the citrulline-NO cycle). This study demonstrates for the first time that the citrulline-NO cycle is induced in FACS-purified rat beta cells exposed to interleukin-1beta(IL-1beta) and that extracellular arginine or citrulline is required for NO production by beta cells. Moreover, the accumulation of arginine was higher in IL-1beta-treated beta cells than in control cells.beta cells expressed mRNAs for the two y+CAT transporters CAT-2A and CAT-2B with no change in transporter expression after exposure to IL-1beta. It is concluded that the activation of the citrulline-NO cycle and an increase in arginine accumulation may be adaptive responses in cytokine-exposed beta-cells to assure an adequate arginine supply for continuous NO production in the presence of low extracellular arginine levels which may prevail during insulitis.
- Subjects :
- Male
Amino Acid Transport Systems
Arginine
Immunology
Nitric Oxide Synthase Type II
Protein degradation
Nitric Oxide
Biochemistry
Nitric oxide
Islets of Langerhans
chemistry.chemical_compound
medicine
Citrulline
Animals
Immunology and Allergy
Amino Acids
Rats, Wistar
Molecular Biology
Cells, Cultured
biology
Reverse Transcriptase Polymerase Chain Reaction
Lysine
Pancreatic islets
Biological Transport
Hematology
medicine.disease
Rats
Cell biology
Nitric oxide synthase
medicine.anatomical_structure
chemistry
biology.protein
Nitric Oxide Synthase
Beta cell
Carrier Proteins
Insulitis
Interleukin-1
Subjects
Details
- ISSN :
- 10434666
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Cytokine
- Accession number :
- edsair.doi.dedup.....6e4dad9bedf1cffe173c3ffc74423c4e