ADMINISTRATION OF A NITRIC-OXIDE SYNTHASE INHIBITOR DOES NOT SUPPRESSLOW-DOSE STREPTOZOTOCIN-INDUCED DIABETES IN MICE

Nitric oxide (NO) has been reported as being a key mediator of the aut oimmune destruction of B-cells in type I diabetes, and studies have de scribed a suppression of low-dose streptozotocin-induced (LDS) diabete s in mice after the use of NO synthase inhibitors. However, these stud ies disagree with regard to the outcome of hyperglycemia and insulitis after treatment with these L-arginine analogs. The present study trie s to clarify this topic by administering N-nitro-L-arginine-methyleste r (NAME) (15 mg/d/mouse/15 d) after an LDS treatment in 108 male C57BL 6/J mice. Glycemia measured at the end of the NAME treatment did show a slight, but significant, reduction when compared to LDS control anim als (p < 0.001), but values returned to diabetic levels 2 wk after wit hdrawal of NAME. Morphological observations demonstrated that the degr ee of infiltration and islet B-cell damage was absolutely not inhibite d by NAME. In conclusion, treatment with L-arginine analogs is not cap able of protecting mice from LDS-induced diabetes.