The Effect of Lifestyle-induced Hepatic Steatosis on Glucagon-stimulated Amino Acid Turnover
Status:
Recruiting
Trial end date:
2021-12-09
Target enrollment:
Participant gender:
Summary
Many patients with type 2 diabetes exhibit elevated plasma concentrations of the
glucose-mobilising pancreatic hormone glucagon; i.e. hyperglucagonaemia. This contributes to
the hyperglycaemic state of the patients and is considered an important component in the
pathophysiology of type 2 diabetes; but the mechanisms underlying this phenomenon remain
unclear. The liver constitutes the main target organ of glucagon, and studies have shown that
hyperglucagonaemia goes hand in hand with hyperaminoacidaemia and that both are associated
with non-alcoholic fatty liver disease (NAFLD), independently of the presence of type 2
diabetes. In line with this, several recent studies support the existence of a feedback-cycle
between the liver and the pancreatic alpha cells, governed by circulating glucagon and amino
acids. The investigators hypothesise that the presence of hepatic steatosis results in
hepatic glucagon resistance at the level of amino acid turnover, i.e. impaired
glucagon-induced suppression of circulating amino acid concentrations. If this hypothesis
proves correct, it would establish build-up of fat in the liver as a core mechanism
underlying hyperglucagonaemia and, since the hyperglucagonemia is at least partly responsible
for the fasting hyperglycaemia, as an important contributor to the hyperglycaemia of type 2
diabetes.
Phase:
N/A
Details
Lead Sponsor:
Malte Palm Suppli, MD
Collaborators:
Clinical Metabolomics Core Facility, Department of Clinical, Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark Department of Biomedical Sciences & NNF Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health, and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Denmark