title: Suppression of low dose streptozotocin induced diabetes in mice by administration of a nitric oxide synthase inhibitor.
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.
authors.affiliation: Diabetes-Forschungsinstitut, Düsseldorf, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Kolb
authors.forename: U
authors.initials: U
authors.lastname: Kiesel
authors.forename: K D
authors.initials: KD
authors.lastname: Kröncke
authors.forename: V
authors.initials: V
authors.lastname: Kolb-Bachofen
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000187:drug effects / Q000276:immunology; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D001786:Blood Glucose; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D019331:NG-Nitroarginine Methyl Ester