The effects of a selective rise in hepatic sinusoidal
norepinephrine on hepatic glucose production are solely attributable
to an increase in glycogenolysis.
Chu, Chang An, Dana K. Sindelar, Doss W. Neal, Eric J. Allen, E.
Patrick Donahue, and Alan D. Cherrington.
Department of Molecular Physiology and Biophysics, Vanderbilt,
University School of Medicine, Nashville, Tennessee 37232-0615
APStracts 4:0226E, 1997.
In order to determine the effect of a selective rise in liver
sinusoidal norepinephrine (NE) on hepatic glucose production (HGP),
norepinephrine (50 ng/kg.min) was infused intraportally (Po-NE) for
3h into five 18-h-fasted conscious dogs maintained on a pancreatic
clamp with basal insulin and glucagon. In the control protocol, NE
(0.2 ng/kg.min) and glucose were infused peripherally into five dogs
to match the arterial NE and blood glucose levels in the Po-NE group.
HGP and gluconeogenesis (GNG) were assessed using tracer (3H-glucose,
14C-alanine) and arteriovenous difference techniques. Hepatic
sinusoidal NE levels rose from 139 +/- 16 (baseline) to 4154 +/- 559
pg/ml (test period) in the Po-NE group, but did not change (121 +/-
11 to 123 +/- 8 pg/ml, respectively) in the control group. The
arterial norepinephrine levels increased minimally in both the Po-NE
group (188 +/- 24 to 231 +/- 28 pg/ml) and the control group (150 +/-
10 to 206 +/-_ 13 pg/ml). Arterial blood glucose levels in the Po-NE
and the control groups increased from 79 +/- 5 to 93 +/-_ 7 mg/dl and
from 76 +/- 3 to 94 +/- 4 mg/dl, respectively. During the portal
norepinephrine infusion, HGP increased from 1.9 +/- 0.2 to 3.5 +/-
0.4 mg/kg x min (15 min; P < 0.05) and then gradually fell to 2.4
+/-_ 0.4 mg/kg.min by 3h. HGP in the control group did not change
(2.0 +/-_ 0.2 to 2.0 +/-_ 0.2 mg/kg.min) for 15 min but then
gradually fell to 1.1 +/-_ 0.2 mg/kg.min by the end of the study.
Since the fall in HGP from 15 min on was parallel in the two groups,
the effect of NE on HGP (the difference between HGP in the two
groups) did not decline over time (_ 1.4 and _ 1.3 mg/kg.min during
the first and last 30 min of the test period, respectively). Neither
gluconeogenic efficiency (24 +/-_ 4 % to 28 +/-_ 5 %) nor the minimal
(0.14 +/-_ 0.03 to 0.17 +/-_ 0.03 mg/kg.min) or maximal (0.55 +/-_
0.1 to 0.61 +/-_ 0.2 mg/kg x min) gluconeogenic rates were
significantly increased during portal NE infusion. Similarly, the
gluconeogenic parameters failed to change in the control group. In
conclusion, selective elevation in hepatic sinusoidal norepinephrine
significantly increases hepatic glucose production by selectively
stimulating glycogenolysis. Compared with the previously determined
effects of epinephrine or glucagon on HGP, the effect of NE is, on a
molar basis, less potent but sustained over time.
Received 30 June 1997; accepted in final form 1 October 1997.
APS Manuscript Number E306-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 29 October 1997