Abstract
Nitric oxide has recently been identified as the primary toxic effector molecule in the lysis of islet cells by inflammatory macrophages. We show here that N-nitro-L-arginine-methylester (NAME), an inhibitor of endothelial and macrophage NO synthase partially suppresses diabetes development in the low dose streptozotocin induced diabetes model in C57BL/6J mice. Mean blood glucose levels were lower in the group receiving NAME throughout the observation period of 30d (p less than 0.05-0.001). Similar concentrations of NAME as expected in vivo were tested in vitro in macrophage-islet cell cocultures and were found to partially suppress NO production and islet cell lysis. We conclude that NO synthase activity is a pathogenetic factor in diabetes development.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Oxidoreductases / antagonists & inhibitors*
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Animals
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Arginine / analogs & derivatives*
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Arginine / pharmacology
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Blood Glucose / analysis
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Diabetes Mellitus, Experimental / immunology
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Diabetes Mellitus, Experimental / metabolism
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Diabetes Mellitus, Experimental / prevention & control*
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In Vitro Techniques
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Islets of Langerhans / drug effects
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Islets of Langerhans / immunology
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Macrophage Activation / immunology
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Macrophages / drug effects*
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Male
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Mice
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Mice, Inbred C57BL
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NG-Nitroarginine Methyl Ester
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Nitric Oxide / metabolism*
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Nitric Oxide Synthase
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Random Allocation
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Rats
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Rats, Inbred Strains
Substances
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Blood Glucose
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Nitric Oxide
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Arginine
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Nitric Oxide Synthase
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Amino Acid Oxidoreductases
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NG-Nitroarginine Methyl Ester