Generation of nitric oxide from streptozotocin (STZ) in the presence of copper(II) plus ascorbate: implication for the development of STZ-induced diabetes

Biochemical and Biophysical Research Communications
A Tsuji, H Sakurai

Abstract

Streptozotocin (STZ) is widely used as a strong inducer of insulin-dependent diabetes in experimental animals. Although nitric oxide (NO) generation from STZ has been proposed to be responsible for the toxicity of pancreatic B-cells, the mechanism is yet unknown. We found that STZ generates NO in the presence of Cu(II) plus ascorbate. In addition, nicotinamide, which is an antidiabetic agent against STZ, has been found to inhibit NO generation from STZ during the reaction with Cu(II) plus ascorbate. Since rat pancreatic islets contain both ascorbate and Cu at the concentrations of 3.5 mM and 1. 0 nmol/mg protein, respectively, our present results indicate that (1>) NO generation is responsible for the development of STZ-induced diabetes and (2) mechanism for the protection of diabetes by nicotinamide is due to the inhibition of NO generation from STZ through complex formation between nicotinamide and Cu (I), which is reduced by ascorbate.

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Citations

Oct 29, 2002·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Mika KatohYukio Fujimoto
Mar 23, 2006·Proceedings of the National Academy of Sciences of the United States of America·R EldorD Melloul
Dec 27, 2005·Biochemical and Biophysical Research Communications·Clifford TolemanJeffrey E Kudlow
Oct 22, 2013·Nitric Oxide : Biology and Chemistry·Christian OpländerChristoph V Suschek
Oct 6, 2012·Nitric Oxide : Biology and Chemistry·Christian OpländerChristoph V Suschek
Nov 30, 2010·Diabetes Research and Clinical Practice·R G Ahmed
Jan 18, 2005·Calcified Tissue International·J Del Pino-MontesJ M Quesada
Jul 25, 2008·Luminescence : the Journal of Biological and Chemical Luminescence·Knox Van DykeDavid H Van Thiel
Jan 26, 2006·American Journal of Physiology. Endocrinology and Metabolism·Hui-Chen SuJan-Kan Chen
Oct 22, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Salah-Eddine Lamhamedi-CherradiYouhai H Chen
Sep 16, 2000·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Y Y JangC S Lee
Feb 11, 1999·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·I KoyamaT Komoda

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