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Publication
The kinetics of glucagon action on the liver during insulin-induced
hypoglycemia.
Authors Pedersen C, Kraft G, Edgerton DS, Scott M, Farmer B, Smith M, Laneve DC,
Williams PE, Moore LM, Cherrington AD
Submitted By Submitted Externally on 4/30/2020
Status Published
Journal American journal of physiology. Endocrinology and metabolism
Year 2020
Date Published 3/1/2020
Volume : Pages Not Specified : Not Specified
PubMed Reference 32208001
Abstract Glucagon's effect on hepatic glucose production is time dependent under
hyperglycemic conditions, such that after an initial burst of hepatic glucose
production (HGP), it slowly wanes. It is not known whether this is also the case
under hypoglycemic conditions, where an increase in HGP is essential. This
question was addressed using adrenalectomized dogs to avoid the confounding
effects of other counterregulatory hormones. During the study, infusions of
epinephrine and cortisol were given to maintain basal levels. Somatostatin and
insulin (800 µU/kg/min) were infused to induce hypoglycemia. After 30 minutes,
glucagon was infused at a basal rate (1 ng/kg/min, baGGN group, n=5) or a rate
8-fold basal (8 ng/kg/min, hiGGN group, n=5) for 4 hours. Glucose was infused to
match the arterial glucose levels between groups. Our data showed that glucagon
has a biphasic effect on the liver despite hypoglycemia. Hyperglucagonemia
stimulated a rapid, transient peak in HGP (4-fold basal production) over about
60 min which was followed by a slow reduction in HGP to a rate 1.5-fold basal.
During the last two hours of the experiment, elevated glucagon stimulated
glucose production at a rate 5-fold greater than basal glucagon (2.5 vs. 0.5
mg/kg/min, respectively), indicating a sustained effect of the hormone. Of note,
the hypoglycemia-induced rises in norepinephrine and glycerol were smaller in
hiGGN compared to baGGN group despite identical hypoglycemia. This finding
suggests that there is reciprocity between glucagon and the sympathetic nervous
system such that when glucagon is increased the sympathetic nervous response to
hypoglycemia is downregulated.





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