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Effect of hepatic denervation on peripheral insulin sensitivity in conscious dogs

1  Department of Molecular Physiology and Biophysics and 2  Diabetes Research and Training Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 We tested the hypothesis that the loss of hepatic nerves decreases peripheral insulin sensitivity. Surgical hepatic denervation (DN)...

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Published in:American journal of physiology: endocrinology and metabolism 2002-02, Vol.282 (2), p.E286-E296
Main Authors: Moore, Mary Courtney, Satake, Shosuke, Baranowski, Bryan, Hsieh, Po-Shiuan, Neal, Doss W, Cherrington, Alan D
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container_start_page E286
container_title American journal of physiology: endocrinology and metabolism
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creator Moore, Mary Courtney
Satake, Shosuke
Baranowski, Bryan
Hsieh, Po-Shiuan
Neal, Doss W
Cherrington, Alan D
description 1  Department of Molecular Physiology and Biophysics and 2  Diabetes Research and Training Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 We tested the hypothesis that the loss of hepatic nerves decreases peripheral insulin sensitivity. Surgical hepatic denervation (DN) was performed in 22 dogs ~16 days before study; 7 dogs (Sham-Sal) had a sham procedure. A euglycemic hyperinsulinemic (1 mU · kg 1 · min 1 ; arterial insulin 35 ± 1 µU/ml in all dogs) clamp was performed in conscious dogs. From 0 to 90 min of the clamp, all dogs received the same treatment; then the DN dogs were divided into three groups. From 90 to 180 min, DN-PeA ( n  = 7) and DN-PoA ( n  = 7) groups received acetylcholine 2.5 µg · kg 1 · min 1 via peripheral or portal vein, respectively, and DN-Sal ( n  =   8) received no acetylcholine. During 150-180 min, the Sham-Sal, DN-Sal, DN-PeA, and DN-PoA groups exhibited glucose infusion rates of 12.4 ± 0.8, 9.3 ± 0.8 ( P
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Surgical hepatic denervation (DN) was performed in 22 dogs ~16 days before study; 7 dogs (Sham-Sal) had a sham procedure. A euglycemic hyperinsulinemic (1 mU · kg 1 · min 1 ; arterial insulin 35 ± 1 µU/ml in all dogs) clamp was performed in conscious dogs. From 0 to 90 min of the clamp, all dogs received the same treatment; then the DN dogs were divided into three groups. From 90 to 180 min, DN-PeA ( n  = 7) and DN-PoA ( n  = 7) groups received acetylcholine 2.5 µg · kg 1 · min 1 via peripheral or portal vein, respectively, and DN-Sal ( n  =   8) received no acetylcholine. During 150-180 min, the Sham-Sal, DN-Sal, DN-PeA, and DN-PoA groups exhibited glucose infusion rates of 12.4 ± 0.8, 9.3 ± 0.8 ( P < 0.05 vs. Sham-Sal), 9.1 ± 0.1 ( P < 0.05 vs. Sham-Sal), and 12.7 ± 1.6 mg · kg 1 · min 1 ; nonhepatic glucose uptakes of 11.5 ± 0.9, 8.9 ± 0.7 ( P < 0.05   vs. Sham-Sal), 8.6 ± 0.9 ( P < 0.05 vs. Sham-Sal), and 11.9 ± 1.7   mg · kg 1 · min 1 ; net hindlimb glucose uptakes of 18.4 ± 2.1, 13.7 ± 1.1 ( P <   0.05 vs. Sham-Sal), 17.5 ± 1.9, and 16.7 ± 3.2 mg/min; and glucose utilization rates of 14.4 ± 1.4, 10.4 ± 0.8 ( P < 0.05 vs. Sham-Sal), 9.8 ± 0.9 ( P < 0.05 vs. Sham-Sal), and 13.6 ± 1.8 mg · kg 1 · min 1 , respectively. DN caused peripheral insulin resistance, and intraportal but not peripheral acetylcholine restored insulin sensitivity. hepatic nerves; acetylcholine]]></description><identifier>ISSN: 0193-1849</identifier><identifier>EISSN: 1522-1555</identifier><identifier>DOI: 10.1152/ajpendo.00201.2001</identifier><identifier>PMID: 11788359</identifier><language>eng</language><publisher>United States</publisher><subject>Acetylcholine - administration &amp; dosage ; Acetylcholine - pharmacology ; Animals ; Arteries ; Denervation ; Dogs ; Fatty Acids, Nonesterified - blood ; Female ; Gluconeogenesis - physiology ; Glucose - metabolism ; Glycerol - blood ; Hormones - blood ; Infusions, Intravenous ; Insulin - physiology ; Insulin Resistance - physiology ; Lactic Acid - blood ; Liver - innervation ; Liver Circulation - physiology ; Male ; Muscle, Skeletal - physiology ; Nervous System Physiological Phenomena ; Portal Vein</subject><ispartof>American journal of physiology: endocrinology and metabolism, 2002-02, Vol.282 (2), p.E286-E296</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c453t-76e47c94fc762490dbf168737b5f5d5f29c2daa6bfa5cc8c5d4ab3a12dcfb3fc3</citedby><cites>FETCH-LOGICAL-c453t-76e47c94fc762490dbf168737b5f5d5f29c2daa6bfa5cc8c5d4ab3a12dcfb3fc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11788359$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Moore, Mary Courtney</creatorcontrib><creatorcontrib>Satake, Shosuke</creatorcontrib><creatorcontrib>Baranowski, Bryan</creatorcontrib><creatorcontrib>Hsieh, Po-Shiuan</creatorcontrib><creatorcontrib>Neal, Doss W</creatorcontrib><creatorcontrib>Cherrington, Alan D</creatorcontrib><title>Effect of hepatic denervation on peripheral insulin sensitivity in conscious dogs</title><title>American journal of physiology: endocrinology and metabolism</title><addtitle>Am J Physiol Endocrinol Metab</addtitle><description><![CDATA[1  Department of Molecular Physiology and Biophysics and 2  Diabetes Research and Training Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 We tested the hypothesis that the loss of hepatic nerves decreases peripheral insulin sensitivity. Surgical hepatic denervation (DN) was performed in 22 dogs ~16 days before study; 7 dogs (Sham-Sal) had a sham procedure. A euglycemic hyperinsulinemic (1 mU · kg 1 · min 1 ; arterial insulin 35 ± 1 µU/ml in all dogs) clamp was performed in conscious dogs. From 0 to 90 min of the clamp, all dogs received the same treatment; then the DN dogs were divided into three groups. From 90 to 180 min, DN-PeA ( n  = 7) and DN-PoA ( n  = 7) groups received acetylcholine 2.5 µg · kg 1 · min 1 via peripheral or portal vein, respectively, and DN-Sal ( n  =   8) received no acetylcholine. During 150-180 min, the Sham-Sal, DN-Sal, DN-PeA, and DN-PoA groups exhibited glucose infusion rates of 12.4 ± 0.8, 9.3 ± 0.8 ( P < 0.05 vs. Sham-Sal), 9.1 ± 0.1 ( P < 0.05 vs. Sham-Sal), and 12.7 ± 1.6 mg · kg 1 · min 1 ; nonhepatic glucose uptakes of 11.5 ± 0.9, 8.9 ± 0.7 ( P < 0.05   vs. Sham-Sal), 8.6 ± 0.9 ( P < 0.05 vs. Sham-Sal), and 11.9 ± 1.7   mg · kg 1 · min 1 ; net hindlimb glucose uptakes of 18.4 ± 2.1, 13.7 ± 1.1 ( P <   0.05 vs. Sham-Sal), 17.5 ± 1.9, and 16.7 ± 3.2 mg/min; and glucose utilization rates of 14.4 ± 1.4, 10.4 ± 0.8 ( P < 0.05 vs. Sham-Sal), 9.8 ± 0.9 ( P < 0.05 vs. Sham-Sal), and 13.6 ± 1.8 mg · kg 1 · min 1 , respectively. DN caused peripheral insulin resistance, and intraportal but not peripheral acetylcholine restored insulin sensitivity. hepatic nerves; acetylcholine]]></description><subject>Acetylcholine - administration &amp; dosage</subject><subject>Acetylcholine - pharmacology</subject><subject>Animals</subject><subject>Arteries</subject><subject>Denervation</subject><subject>Dogs</subject><subject>Fatty Acids, Nonesterified - blood</subject><subject>Female</subject><subject>Gluconeogenesis - physiology</subject><subject>Glucose - metabolism</subject><subject>Glycerol - blood</subject><subject>Hormones - blood</subject><subject>Infusions, Intravenous</subject><subject>Insulin - physiology</subject><subject>Insulin Resistance - physiology</subject><subject>Lactic Acid - blood</subject><subject>Liver - innervation</subject><subject>Liver Circulation - physiology</subject><subject>Male</subject><subject>Muscle, Skeletal - physiology</subject><subject>Nervous System Physiological Phenomena</subject><subject>Portal Vein</subject><issn>0193-1849</issn><issn>1522-1555</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><recordid>eNp1kF1r2zAUhkXZaNN2f6AXxVe7c6ZPy74cIf2AwBi010KWjmIVx_IkO1v-_ZQlpVcDgcTR-7wcHoTuCF4SIug3_TbCYMMSY4rJkmJMLtAif9CSCCE-oQUmDStJzZsrdJ3SG8ZYCk4v0RUhsq6ZaBbo59o5MFMRXNHBqCdvCgsDxH1-hqHIZ4Toxw6i7gs_pLn3Q5FgSH7yez8d8qwwYUjGhzkVNmzTLfrsdJ_gy_m-Qa8P65fVU7n58fi8-r4pDRdsKmUFXJqGOyMryhtsW0eqWjLZCiescLQx1GpdtU4LY2ojLNct04Ra41rmDLtBX0-9Ywy_ZkiT2vlkoO_1AHkXJQmTVcV5DtJT0MSQUgSnxuh3Oh4UweooUp1Fqn8i1VFkhu7P7XO7A_uBnM3lQHMKdH7b_fYR1Ngdkg992B7Uw9z3L_Bnem-mNVVUrWldqdG6zJb_Z9-X-WDYX2FDl-s</recordid><startdate>20020201</startdate><enddate>20020201</enddate><creator>Moore, Mary Courtney</creator><creator>Satake, Shosuke</creator><creator>Baranowski, Bryan</creator><creator>Hsieh, Po-Shiuan</creator><creator>Neal, Doss W</creator><creator>Cherrington, Alan D</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20020201</creationdate><title>Effect of hepatic denervation on peripheral insulin sensitivity in conscious dogs</title><author>Moore, Mary Courtney ; 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Surgical hepatic denervation (DN) was performed in 22 dogs ~16 days before study; 7 dogs (Sham-Sal) had a sham procedure. A euglycemic hyperinsulinemic (1 mU · kg 1 · min 1 ; arterial insulin 35 ± 1 µU/ml in all dogs) clamp was performed in conscious dogs. From 0 to 90 min of the clamp, all dogs received the same treatment; then the DN dogs were divided into three groups. From 90 to 180 min, DN-PeA ( n  = 7) and DN-PoA ( n  = 7) groups received acetylcholine 2.5 µg · kg 1 · min 1 via peripheral or portal vein, respectively, and DN-Sal ( n  =   8) received no acetylcholine. During 150-180 min, the Sham-Sal, DN-Sal, DN-PeA, and DN-PoA groups exhibited glucose infusion rates of 12.4 ± 0.8, 9.3 ± 0.8 ( P < 0.05 vs. Sham-Sal), 9.1 ± 0.1 ( P < 0.05 vs. Sham-Sal), and 12.7 ± 1.6 mg · kg 1 · min 1 ; nonhepatic glucose uptakes of 11.5 ± 0.9, 8.9 ± 0.7 ( P < 0.05   vs. Sham-Sal), 8.6 ± 0.9 ( P < 0.05 vs. Sham-Sal), and 11.9 ± 1.7   mg · kg 1 · min 1 ; net hindlimb glucose uptakes of 18.4 ± 2.1, 13.7 ± 1.1 ( P <   0.05 vs. Sham-Sal), 17.5 ± 1.9, and 16.7 ± 3.2 mg/min; and glucose utilization rates of 14.4 ± 1.4, 10.4 ± 0.8 ( P < 0.05 vs. Sham-Sal), 9.8 ± 0.9 ( P < 0.05 vs. Sham-Sal), and 13.6 ± 1.8 mg · kg 1 · min 1 , respectively. DN caused peripheral insulin resistance, and intraportal but not peripheral acetylcholine restored insulin sensitivity. hepatic nerves; acetylcholine]]></abstract><cop>United States</cop><pmid>11788359</pmid><doi>10.1152/ajpendo.00201.2001</doi></addata></record>
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source American Physiological Society Journals
subjects Acetylcholine - administration & dosage
Acetylcholine - pharmacology
Animals
Arteries
Denervation
Dogs
Fatty Acids, Nonesterified - blood
Female
Gluconeogenesis - physiology
Glucose - metabolism
Glycerol - blood
Hormones - blood
Infusions, Intravenous
Insulin - physiology
Insulin Resistance - physiology
Lactic Acid - blood
Liver - innervation
Liver Circulation - physiology
Male
Muscle, Skeletal - physiology
Nervous System Physiological Phenomena
Portal Vein
title Effect of hepatic denervation on peripheral insulin sensitivity in conscious dogs
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