title: Administration of a nitric oxide synthase inhibitor does not suppress low-dose streptozotocin-induced diabetes in mice.
abstract: Nitric oxide (NO) has been reported as being a key mediator of the autoimmune destruction of B-cells in type I diabetes, and studies have described a suppression of low-dose streptozotocin-induced (LDS) diabetes in mice after the use of NO synthase inhibitors. However, these studies disagree with regard to the outcome of hyperglycemia and insulitis after treatment with these L-arginine analogs. The present study tries to clarify this topic by administering N-nitro-L-arginine-methylester (NAME) (15 mg/d/mouse/15 d) after an LDS treatment in 108 male C57BL6/J mice. Glycemia measured at the end of the NAME treatment did show a slight, but significant, reduction when compared to LDS control animals (p < 0.001), but values returned to diabetic levels 2 wk after withdrawal of NAME. Morphological observations demonstrated that the degree of infiltration and islet B-cell damage was absolutely not inhibited by NAME. In conclusion, treatment with L-arginine analogs is not capable of protecting mice from LDS-induced diabetes.
authors.affiliation: Institute of Anatomy, School of Medicine, 2nd University of Naples, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Papaccio
authors.forename: V
authors.initials: V
authors.lastname: Esposito
authors.forename: M V
authors.initials: MV
authors.lastname: Latronico
authors.forename: F A
authors.initials: FA
authors.lastname: Pisanti
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D013311:Streptozocin
chemical_list: D001786:Blood Glucose; D004791:Enzyme Inhibitors; D013311:Streptozocin; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester