Role of the hepatic sympathetic nerves in the regulation of net hepatic glucose uptake and the mediation of the portal glucose signal

Role of the hepatic sympathetic nerves in the regulation of net hepatic glucose uptake and the... Portal glucose delivery enhances net hepatic glucose uptake (NHGU) relative to peripheral glucose delivery. We hypothesize that the sympathetic nervous system normally restrains NHGU, and portal glucose delivery relieves the inhibition. Two groups of 42-h-fasted conscious dogs were studied using arteriovenous difference techniques. Denervated dogs (DEN; n = 10) underwent selective sympathetic denervation by cutting the nerves at the celiac nerve bundle near the common hepatic artery; control dogs (CON; n = 10) underwent a sham procedure. After a 140-min basal period, somatostatin was given along with basal intraportal infusions of insulin and glucagon. Glucose was infused peripherally to double the hepatic glucose load (HGL) for 90 min ( P1 ). In P2 , glucose was infused intraportally (3–4 mg·kg –1 ·min –1 ), and the peripheral glucose infusion was reduced to maintain the HGL for 90 min. This was followed by 90 min ( P3 ) in which portal glucose infusion was terminated and peripheral glucose infusion was increased to maintain the HGL. P1 and P3 were averaged as the peripheral glucose infusion period (PE). The average HGLs (mg·kg –1 ·min –1 ) in CON and DEN were 55 ± 3 and 54 ± 4 in the peripheral periods and 55 ± 3 and 55 ± 4 in P2 , respectively. The arterial insulin and glucagon levels remained basal in both groups. NHGU (mg·kg –1 ·min –1 ) in CON averaged 1.7 ± 0.3 during PE and increased to 2.9 ± 0.3 during P2 . NHGU (mg·kg –1 ·min –1 ) was greater in DEN than CON ( P < 0.05) during PE (2.9 ± 0.4) and failed to increase significantly (3.2 ± 0.2) during P2 (not significant vs. CON). Selective sympathetic denervation increased NHGU during hyperglycemia but significantly blunted the response to portal glucose delivery. autonomic nervous system; liver; canine Address for reprint requests and other correspondence: C. DiCostanzo, Dept. of Molecular Physiology and Biophysics, 710 Medical Research Bldg. I (RRB), Vanderbilt Univ. Medical School, Nashville, TN 37232-0615 (e-mail: Catherine.dicostanzo@vanderbilt.edu ) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Endocrinology and Metabolism The American Physiological Society

Role of the hepatic sympathetic nerves in the regulation of net hepatic glucose uptake and the mediation of the portal glucose signal

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Publisher
The American Physiological Society
Copyright
Copyright © 2011 the American Physiological Society
ISSN
0193-1849
eISSN
1522-1555
D.O.I.
10.1152/ajpendo.00184.2005
Publisher site
See Article on Publisher Site

Abstract

Portal glucose delivery enhances net hepatic glucose uptake (NHGU) relative to peripheral glucose delivery. We hypothesize that the sympathetic nervous system normally restrains NHGU, and portal glucose delivery relieves the inhibition. Two groups of 42-h-fasted conscious dogs were studied using arteriovenous difference techniques. Denervated dogs (DEN; n = 10) underwent selective sympathetic denervation by cutting the nerves at the celiac nerve bundle near the common hepatic artery; control dogs (CON; n = 10) underwent a sham procedure. After a 140-min basal period, somatostatin was given along with basal intraportal infusions of insulin and glucagon. Glucose was infused peripherally to double the hepatic glucose load (HGL) for 90 min ( P1 ). In P2 , glucose was infused intraportally (3–4 mg·kg –1 ·min –1 ), and the peripheral glucose infusion was reduced to maintain the HGL for 90 min. This was followed by 90 min ( P3 ) in which portal glucose infusion was terminated and peripheral glucose infusion was increased to maintain the HGL. P1 and P3 were averaged as the peripheral glucose infusion period (PE). The average HGLs (mg·kg –1 ·min –1 ) in CON and DEN were 55 ± 3 and 54 ± 4 in the peripheral periods and 55 ± 3 and 55 ± 4 in P2 , respectively. The arterial insulin and glucagon levels remained basal in both groups. NHGU (mg·kg –1 ·min –1 ) in CON averaged 1.7 ± 0.3 during PE and increased to 2.9 ± 0.3 during P2 . NHGU (mg·kg –1 ·min –1 ) was greater in DEN than CON ( P < 0.05) during PE (2.9 ± 0.4) and failed to increase significantly (3.2 ± 0.2) during P2 (not significant vs. CON). Selective sympathetic denervation increased NHGU during hyperglycemia but significantly blunted the response to portal glucose delivery. autonomic nervous system; liver; canine Address for reprint requests and other correspondence: C. DiCostanzo, Dept. of Molecular Physiology and Biophysics, 710 Medical Research Bldg. I (RRB), Vanderbilt Univ. Medical School, Nashville, TN 37232-0615 (e-mail: Catherine.dicostanzo@vanderbilt.edu )

Journal

AJP - Endocrinology and MetabolismThe American Physiological Society

Published: Jan 1, 2006

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