Insulin resistance caused by hepatic cholinergic interruption and
reversed by acetylcholine administration.
Xie, Hongsheng, and W. Wayne Lautt.
DEPARTMENT OF PHARMACOLOGY & THERAPEUTICS, FACULTY OF MEDICINE,
UNIVERSITY OF MANITOBA, WINNIPEG, MANITOBA, CANADA, R3E OW3
APStracts 3:0092E, 1996.
The role of hepatic parasympathetic nerves on insulin effectiveness
was evaluated in fed anesthetized rats. Insulin sensitivity was
assessed using a modified euglycemic clamp to quantitate the amount
of glucose required to maintain euglycemia over 60 minutes following
administration of insulin (50 mU/kg). With normal innervation,
intraportal infusions of acetylcholine (Ach, 2.5 [mu]g/kg/min) did
not alter insulin sensitivity but atropine (3 mg/kg i.p.v.) reduced
insulin sensitivity (49.4 + 5.8%, p<0.001, n=7). Liver
denervation resulted in reduction of insulin responsiveness by 70.8 +
5.8% (p<0.001, n=8) which was fully (96.8 + 12.5%) reversed by
Ach. Ach into the portal vein reversed insulin resistance produced by
denervation but intravenous Ach was without effect thus showing that
the liver was the site of Ach action. Regression analysis suggests
that some component of insulin response is not dependent on hepatic
cholinergic nerve effects but that virtually all of the variability
in response to insulin in normal fed rats tested under these
conditions could be accounted for by variability in the hepatic
parasympathetic-dependent insulin sensitivity. These data suggest a
major role for hepatic parasympathetic nerves in regulation of whole
body clearance of glucose in response to insulin.
Received 21 December 1995; accepted in final form 15 April 1996.
APS Manuscript Number E606-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 May 96