Insulin sensitivity is mediated by the activation of the ACh/NO/cGMP pathway in rat liver

American Journal of Physiology. Gastrointestinal and Liver Physiology
Maria P GuarinoM Paula Macedo

Abstract

The hepatic parasympathetic nerves and hepatic nitric oxide synthase (NOS) are involved in the secretion of a hepatic insulin sensitizing substance (HISS), which mediates peripheral insulin sensitivity. We tested whether binding of ACh to hepatic muscarinic receptors is an upstream event to the synthesis of nitric oxide (NO), which, along with the activation of hepatic guanylate cyclase (GC), permits HISS release. Male Wistar rats (8-9 wk) were anesthetized with pentobarbital sodium (65 mg/kg). Insulin sensitivity was assessed using a euglycemic clamp [the rapid insulin sensitivity test (RIST)]. HISS inhibition was induced by antagonism of muscarinic receptors (atropine, 3 mg/kg i.v.) or by blockade of NOS [NG-nitro-L-arginine methyl ester (L-NAME), 1 mg/kg intraportally (i.p.v.)]. After the blockade, HISS action was tentatively restored using a NOdonor [3-morpholynosydnonimine (SIN-1), 5-10 mg/kg i.p.v.] or ACh (2.5-5 microg.kg(-1).min(-1) .i.p.v.). SIN-1 (10 mg/kg) reversed the inhibition caused by atropine (RIST postatropine 137.7 +/- 8.3 mg glucose/kg; reversed to 288.3 +/- 15.5 mg glucose/kg, n = 6) and by L-NAME (RIST post-L-NAME 152.2 +/- 21.3 mg glucose/kg; reversed to 321.7 +/- 44.7 mg glucose/kg, n = 5). ACh did not r...Continue Reading

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Dec 6, 2002·American Journal of Physiology. Gastrointestinal and Liver Physiology·Maria P GuarinoM Paula Macedo

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Citations

Jul 3, 2010·The British Journal of Nutrition·Ricardo A AfonsoM Paula Macedo
Jun 19, 2008·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Rogério Tavares RibeiroMaria Paula Macedo
May 16, 2012·Advances in Nutrition·Mary Courtney MooreAlan D Cherrington
Nov 1, 2013·Reviews in Endocrine & Metabolic Disorders·Maria Paula MacedoRogério T Ribeiro
Dec 18, 2008·Canadian Journal of Physiology and Pharmacology·Rita S PatarrãoM Paula Macedo
Jun 15, 2012·Canadian Journal of Physiology and Pharmacology·Ana B FernandesM Paula Macedo
Jun 20, 2012·Canadian Journal of Physiology and Pharmacology·Rita S PatarrãoM Paula Macedo
Mar 6, 2013·Canadian Journal of Physiology and Pharmacology·Kawshik K ChowdhuryW Wayne Lautt
Jul 6, 2013·Canadian Journal of Physiology and Pharmacology·Frédéric BourgoinMaryse Pitre
Jan 1, 2014·Journal of Clinical Medicine·W Wayne Lautt, Hui Helen Wang
Oct 18, 2012·Fish & Shellfish Immunology·Qiufen JiangLinsheng Song
Jan 17, 2007·Metabolism: Clinical and Experimental·R T RibeiroM Paula Macedo
Feb 24, 2006·British Journal of Pharmacology·Maria P Guarino, M Paula Macedo
Jun 1, 2014·Free Radical Biology & Medicine·Brian E Sansbury, Bradford G Hill
Oct 14, 2011·Acta Cirúrgica Brasileira·Lanese Medeiros FigueiredoSérgio Botelho Guimarães
Sep 21, 2011·Experimental Biology and Medicine·Adelson M RodriguesElisa M S Higa
Dec 12, 2012·Journal of Cardiovascular Pharmacology and Therapeutics·Sean Jedrzkiewicz, John D Parker
Jan 9, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hui Helen WangW Wayne Lautt
Apr 4, 2007·European Journal of Mass Spectrometry·Celina SantosJorge Caldeira
May 12, 2015·PloS One·Rita S PatarrãoM Paula Macedo
Feb 6, 2010·The Journal of Pharmacology and Experimental Therapeutics·Joshua SchaferW Wayne Lautt
Nov 28, 2007·Experimental Biology and Medicine·Clemence BlouetJean-François Huneau
Sep 19, 2020·Antioxidants·Inês Sousa-LimaM Paula Macedo

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