Reduction of insulin-stimulated glucose uptake by peroxynitrite is concurrent with tyrosine nitration of insulin receptor substrate-1

Biochemical and Biophysical Research Communications
Takashi NomiyamaHirotaka Watada

Abstract

Inducible nitric oxide synthetase plays an essential role in insulin resistance induced by a high-fat diet. The reaction of nitric oxide with superoxide leads to the formation of peroxynitrite (ONOO-), which can modify several proteins. In this study, we investigated whether peroxynitrite impairs insulin-signalling pathway. Our experiments showed that 3-(4-morpholinyl)sydnonimine hydrochloride (SIN-1), a constitutive producer of peroxynitrite, dose-dependently inhibited insulin-stimulated glucose uptake. While SIN-1 did not affect the insulin receptor protein level and tyrosine phosphorylation, it reduced the insulin receptor substrate-1 (IRS-1) protein level, and IRS-1 associated phosphatidylinositol-3 kinase (PI-3 kinase) activity. Although SIN-1 did not induce Ser307 phosphorylation of IRS-1, tyrosine nitration of IRS-1 was detected in SIN-1-treated-Rat1 fibroblasts expressing human insulin receptors. Mass spectrometry showed that peroxynitrite induced at least four nitrated tyrosine residues in rat IRS-1, including Tyr939, which is critical for association of IRS-1 with the p85 subunit of PI-3 kinase. Our results suggest that peroxynitrite reduces the IRS-1 protein level and decreases phosphorylation of IRS-1 concurrent wit...Continue Reading

Citations

Aug 2, 2007·Nature Reviews. Drug Discovery·Csaba SzabóRafael Radi
Jul 7, 2005·Antioxidants & Redox Signaling·Ashok K Srivastava
Nov 19, 2008·Antioxidants & Redox Signaling·M Carmen Martínez, Ramaroson Andriantsitohaina
Jul 26, 2012·American Journal of Physiology. Endocrinology and Metabolism·Michael J BodenEdward W Kraegen
Jan 24, 2007·Physiological Reviews·Pál PacherLucas Liaudet
Mar 11, 2009·Frontiers in Bioscience (Landmark Edition)·Lucas LiaudetPal Pacher
Nov 9, 2014·Journal of Molecular Endocrinology·Jun ZhouMing-Hui Zou
Jul 2, 2008·The Journal of Physiology·Hervé DuplainUrs Scherrer
Mar 8, 2016·Life Sciences·Ines Elbini DhouibMohamed Montassar Lasram
Oct 27, 2009·Trends in Endocrinology and Metabolism : TEM·Dorit Samocha-BonetLesley V Campbell
Aug 18, 2009·Toxicology and Applied Pharmacology·Jun Zhou, Kaixun Huang
Oct 15, 2008·Placenta·R P WebsterL Myatt
Aug 9, 2005·Seminars in Pediatric Surgery·Jeffrey S UppermanHenri R Ford
Nov 20, 2014·Cardiovascular Diabetology·Yuichi TerawakiToshihiko Yanase
Nov 27, 2008·Alcoholism, Clinical and Experimental Research·Vishnudutt PurohitByoung-Joon Song
Oct 1, 2013·Free Radical Biology & Medicine·Wataru AoiToshikazu Yoshikawa
Jan 26, 2013·Diabetes·Kyoichiro Tsuchiya, Domenico Accili
Sep 17, 2008·Clinical Biochemistry·Edimar Cristiano PereiraDulcineia Saes Parra Abdalla
Sep 5, 2013·Diabetes & Vascular Disease Research : Official Journal of the International Society of Diabetes and Vascular Disease·Anna C Roberts, Karen E Porter
Nov 17, 2015·Experimental Biology and Medicine·Marzena WojcikLucyna Alicja Wozniak
Oct 30, 2008·Diabetes & Vascular Disease Research : Official Journal of the International Society of Diabetes and Vascular Disease·Antonio Ceriello
Dec 1, 2006·The Journal of Biological Chemistry·Toyoyoshi UchidaHirotaka Watada
Sep 30, 2010·American Journal of Physiology. Endocrinology and Metabolism·Phillip J WhiteAndré Marette
Jul 14, 2011·Dalton Transactions : an International Journal of Inorganic Chemistry·Aviva Levina, Peter A Lay
Jan 8, 2020·Cell Biology International·Mariya SabadashkaNataliia Sybirna
Apr 16, 2016·British Journal of Pharmacology·Aleksandra JankovicBato Korac
Oct 9, 2020·Yeungnam University Journal of Medicine·Soyoung Park, So-Young Park
Jun 30, 2009·Archives of Biochemistry and Biophysics·Jun ZhouKaixun Huang

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