J Physiol Society Meetings
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

J Physiol Volume 584, Number 3, 921-933, November 1, 2007 DOI: 10.1113/jphysiol.2007.140277
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental data
Right arrow All Versions of this Article:
584/3/921    most recent
jphysiol.2007.140277v1
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Vasilijevic, A.
Right arrow Articles by Korac, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vasilijevic, A.
Right arrow Articles by Korac, B.
Related Collections
Right arrow Renal and Endocrine

RENAL AND ENDOCRINE

Beneficial effects of L-arginine–nitric oxide-producing pathway in rats treated with alloxan

 Ana Vasilijevic1, Biljana Buzadzic1, Aleksandra Korac2, Vesna Petrovic1, Aleksandra Jankovic1 and Bato Korac1

1 Department of Physiology, Institute for Biological Research, ‘Sinisa Stankovic’, University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia
2 Institute of Zoology, Faculty of Biology, University of Belgrade, Studentski trg 16, 11000 Belgrade, Serbia

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.

(Received 6 July 2007; accepted after revision 21 August 2007; first published online 23 August 2007)
Corresponding author B. Korac: University of Belgrade, Institute for Biological Research, ‘Sinisa Stankovic’, Department of Physiology, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia. Email: koracb{at}ibiss.bg.ac.yu

This paper has online supplemental material.






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2007 The Physiological Society.