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Region Hovedstaden - en del af Københavns Universitetshospital
E-pub ahead of print

Glucagon Resistance at the Level of Amino Acid Turnover in Obese Subjects with Hepatic Steatosis

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DOI

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Vis graf over relationer

Glucagon secretion is regulated by circulating glucose, but it has turned out that amino acids also play an important role, and that hepatic amino acid metabolism and glucagon are linked in a mutual feed-back cycle, the liver-alpha cell axis. On this background, we hypothesized that hepatic steatosis might impair glucagon's action on hepatic amino acid metabolism and lead to hyperaminoacidemia and hyperglucagonemia.We subjected 15 healthy lean and 15 obese steatotic male participants to a pancreatic clamp with somatostatin and evaluated hepatic glucose and amino acid metabolism during basal and high physiological levels of glucagon. The degree of steatosis was evaluated from liver biopsies.Total RNA sequencing of liver biopsies revealed perturbations in the expression of genes predominantly involved in amino acid metabolism in the obese steatotic individuals. This group was also characterized by fasting hyperglucagonemia, hyperaminoacidemia and an absent lowering of amino acid levels in response to high levels of glucagon. Endogenous glucose production was similar between lean and obese individuals.Our results suggest that hepatic steatosis causes resistance to the effect of glucagon on amino acid metabolism resulting in increased amino acid concentrations as well as increased glucagon secretion providing a likely explanation of fatty liver-associated hyperglucagonemia.

OriginalsprogEngelsk
Artikelnummerdb190715
TidsskriftDiabetes
ISSN0012-1797
DOI
StatusE-pub ahead of print - 23 jan. 2020

Bibliografisk note

© 2020 by the American Diabetes Association.

ID: 59248064