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Publication
The Importance of the Mechanisms by Which Insulin Regulates Meal-Associated
Liver Glucose Uptake in the Dog.
Authors Kraft G, Coate KC, Smith M, Farmer B, Scott M, Cherrington AD, Edgerton DS
Submitted By Submitted Externally on 12/3/2021
Status Published
Journal Diabetes
Year 2021
Date Published 6/1/2021
Volume : Pages 70 : 1292 - 1302
PubMed Reference 33757993
Abstract Hepatic glucose uptake (HGU) is critical for maintaining normal postprandial
glucose metabolism. Insulin is clearly a key regulator of HGU, but the
physiologic mechanisms by which it acts have yet to be established. This study
sought to determine the mechanisms by which insulin regulates liver glucose
uptake under postprandial-like conditions (hyperinsulinemia, hyperglycemia, and
a positive portal vein-to-arterial glucose gradient). Portal vein insulin
infusion increased hepatic insulin levels fivefold in healthy dogs. In one group
(n = 7), the physiologic response was allowed to fully occur, while in another
(n = 7), insulin's indirect hepatic effects, occurring secondary to its actions
on adipose tissue, pancreas, and brain, were blocked. This was accomplished by
infusing triglyceride (intravenous), glucagon (portal vein), and inhibitors of
brain insulin action (intracerebroventricular) to prevent decreases in plasma
free fatty acids or glucagon, while blocking increased hypothalamic insulin
signaling for 4 h. In contrast to the indirect hepatic effects of insulin, which
were previously shown capable of independently generating a half-maximal
stimulation of HGU, direct hepatic insulin action was by itself able to fully
stimulate HGU. This suggests that under hyperinsulinemic/hyperglycemic
conditions insulin's indirect effects are redundant to direct engagement of
hepatocyte insulin receptors.




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