Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Circulating Metabolites and Lipids Are Associated to Diabetic Retinopathy in Individuals With Type 1 Diabetes

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. GIP and GLP-1 Potentiate Sulfonylurea-Induced Insulin Secretion in Hepatocyte Nuclear Factor 1-Alpha Mutation Carriers

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Epigenome-wide association study of incident type 2 diabetes in a British population: EPIC-Norfolk study

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Lean women with polycystic ovary syndrome and insulin resistance have normal incretin effect, which is unaffected by metformin therapy

    Publikation: Bidrag til tidsskriftKonferenceabstrakt i tidsskriftForskningpeer review

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 feedback cycle, the liver-α-cell axis. On the basis of this knowledge, 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 when glucagon was at basal levels and at high physiological levels. The degree of steatosis was evaluated from liver biopsy specimens. Total RNA sequencing of liver biopsy specimens from the obese steatotic individuals revealed perturbations in the expression of genes predominantly involved in amino acid metabolism. This group was characterized by fasting hyperglucagonemia, hyperaminoacidemia, and no 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. This results in increased amino acid concentrations and increased glucagon secretion, providing a likely explanation for fatty liver-associated hyperglucagonemia.

OriginalsprogEngelsk
Artikelnummerdb190715
TidsskriftDiabetes
Vol/bind69
Udgave nummer6
Sider (fra-til)1090-1099
Antal sider10
ISSN0012-1797
DOI
StatusUdgivet - jun. 2020

Bibliografisk note

© 2020 by the American Diabetes Association.

ID: 59248064