This paper has online supplemental material.
Beneficial effects of L-arginine–nitric oxide-producing pathway in rats treated with alloxan
Article first published online: 31 OCT 2007
The Journal of Physiology
Volume 584, Issue 3, pages 921–933, November 2007
How to Cite
Vasilijević, A., Buzadžić, B., Korać, A., Petrović, V., Janković, A. and Korać, B. (2007), Beneficial effects of L-arginine–nitric oxide-producing pathway in rats treated with alloxan. The Journal of Physiology, 584: 921–933. doi: 10.1113/jphysiol.2007.140277
- Issue published online: 31 OCT 2007
- Article first published online: 31 OCT 2007
- (Resubmitted 6 July 2007; accepted after revision 21 August 2007; first published online 23 August 2007)
In an attempt to elucidate molecular mechanisms and factors involved in β cell regeneration, we evaluated a possible role of the l-arginine–nitric oxide (NO)-producing pathway in alloxan-induced diabetes mellitus. Diabetes was induced in male Mill Hill rats with a single alloxan dose (120 mg kg−1). Both non-diabetic and diabetic groups were additionally separated into three subgroups: (i) receiving l-arginine · HCl (2.25%), (ii) receiving l-NAME · HCl (0.01%) for 12 days as drinking liquids, and (iii) control. Treatment of diabetic animals started after diabetes induction (glucose level ≥ 12 mmol l−1). We found that disturbed glucose homeostasis, i.e. blood insulin and glucose levels in diabetic rats was restored after l-arginine treatment. Immunohistochemical findings revealed that l-arginine had a favourable effect on β cell neogenesis, i.e. it increased the area of insulin-immunopositive cells. Moreover, confocal microscopy showed colocalization of insulin and pancreas duodenum homeobox-1 (PDX-1) in both endocrine and exocrine pancreas. This increase in insulin-expressing cells was accompanied by increased cell proliferation (observed by proliferating cell nuclear antigen-PCNA immunopositivity) which occurred in a regulated manner since it was associated with increased apoptosis (detected by the TUNEL method). Furthermore, l-arginine enhanced both nuclear factor-kB (NF-kB) and neuronal nitric oxide synthase (nNOS) immunopositivities. The effect of l-arginine on antioxidative defence was observed especially in restoring to control level the diabetes-induced increase in glutathione peroxidase activity. In contrast to l-arginine, diabetic pancreas was not affected by l-NAME supplementation. In conclusion, the results suggest beneficial l-arginine effects on alloxan-induced diabetes resulting from the stimulation of β cell neogenesis, including complex mechanisms of transcriptional and redox regulation.