Physiologic changes in circulating glucagon alter hepatic glucose
disposition during portal glucose delivery.
Holste, Linda C., Cynthia C. Connolly, Mary Courtney Moore, Doss W.
Neal, and Alan D. Cherrington.
Departments of Molecular Physiology & Biophysics, and Diabetes
Research and Training Center, Vanderbilt University School of
Medicine, Nashville, TN 37232
APStracts 4:0109E, 1997.
Plasma glucagon declines in response to feedings of pure glucose and
often rises in response to mixed meals. The aim of this study was to
determine whether physiologic changes in glucagon can alter the rate
of net hepatic glucose uptake (NHGU) or glycogen synthesis under
metabolic conditions commonly present postprandially (hyperglycemia,
hyperinsulinemia, and portal vein glucose concentrations exceeding
those in the arterial circulation). Somatostatin was infused into two
groups of conscious 42-h-fasted dogs (n=6/group), insulin and
glucagon were replaced intraportally at basal rates, and a peripheral
infusion of glucose was used to create hyperglycemia (hepatic glucose
load 2-fold basal) for 90 min (Period 1). Then for 240 min (Period 2)
the insulin infusion was increased 4-fold, glucose was infused
intraportally and peripherally, the hepatic glucose load was
maintained equivalent to that in Period 1, and glucagon was infused
to sustain immunoreactive glucagon levels 50% above basal (HiGGN
group) or to reduce glucagon values progressively to a level 40%
below basal (LoGGN group). Rates of NHGU (mg.kg-1.min-1) were very
low during Period 1 (- 0.9+/-0.7 in LoGGN vs -0.2+/-0.4 in HiGGN, NS)
but increased in both groups during Period 2 (- 4.1+/-0.6 vs -1.9+/
-0.2 in LoGGN and HiGGN, respectively, p<0.05). Endogenous Ra (Endo
Ra) declined significantly during Period 2 in LoGGN (p<0.01 vs
basal), but did not change significantly in HiGGN. Tracer-determined
hepatic glucose uptake did not differ between the two groups. The
increment in liver glycogen synthase I (12.5+/-3% v 6.5+/-2% of
total) evident at the end of study was greater in LoGGN (p<0.05),
as was net hepatic glycogen synthesis (27+/-8 vs 13+/-3 mg/g liver,
p=0.06). An elevation in glucagon significantly reduced NHGU and the
activation of glycogen synthase and tended to reduce glycogen
deposition. The decrease in NHGU resulted from a failure to suppress
Endo Ra.
Received 13 December 1996; accepted in final form 25 April 1997.
APS Manuscript Number E611-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 13 May 1997