NCT04859322

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

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 20 (actual)
• Sponsor: Malte Palm Suppli, MD · Academic / Other
• Sex: Male
• Age: 20 Years – 65 Years
• Healthy volunteers: Accepted

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

Type	Name	Description
DRUG	Glucagon	Pancreatic clamp

Timeline

• Start date: 2021-02-08
• Primary completion: 2021-12-09
• Completion: 2021-12-09
• First posted: 2021-04-26
• Last updated: 2023-05-11

Locations

1 site across 1 country: Denmark