The Effect of Lifestyle-induced Hepatic Steatosis on Glucagon-stimulated Amino Acid Turnover

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.

Conditions

• Non-Alcoholic Fatty Liver Disease
• Glucagon Resistance

Interventions

DRUG

Glucagon

Pancreatic clamp

Sponsors & Collaborators

• Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Denmark

  collaborator UNKNOWN

• Clinical Metabolomics Core Facility, Department of Clinical, Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

  collaborator UNKNOWN

• Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

  collaborator UNKNOWN

• Department of Biomedical Sciences & NNF Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

  collaborator UNKNOWN

• Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health, and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

  collaborator UNKNOWN

• Malte Palm Suppli, MD

  lead OTHER

Study Design

Allocation

NA

Purpose

BASIC_SCIENCE

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

20 Years

Max Age

65 Years

Sex

MALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2021-02-08

Primary Completion

2021-12-09

Completion

2021-12-09

Countries

• Denmark

Study Locations