Development of a glucagon sensitivity test in humans: Pilot data and the GLUSENTIC study protocol

Area of Science:

• Endocrinology
• Metabolic Physiology
• Hepatology

Background:

• The liver-alpha cell axis regulates amino acid and glucose metabolism.
• Non-alcoholic fatty liver disease (NAFLD) is linked to impaired glucagon signaling (glucagon resistance).
• Currently, no human experimental test exists to assess glucagon resistance.

Purpose of the Study:

• To develop and validate an experimental test for assessing human glucagon sensitivity.
• To establish a glucagon sensitivity index related to amino acid catabolism.
• To investigate glucagon sensitivity in individuals with varying BMI and hepatic steatosis.

Main Methods:

• A proposed glucagon sensitivity test involving intravenous glucagon injection and amino acid infusion.
• Development of a glucagon sensitivity index.
• The GLUSENTIC study protocol for applying the test in a cross-sectional study.
• Inclusion of 65 participants with diverse BMI and type 1 diabetes, grouped by hepatic steatosis (MRI).

Main Results:

• Pilot studies informed the development of the glucagon sensitivity test and index.
• The GLUSENTIC study protocol is detailed for application in ongoing research.
• The primary outcome will compare glucagon sensitivity index between individuals with and without hepatic steatosis.

Conclusions:

• A novel glucagon sensitivity test and index have been developed for human use.
• This test may elucidate the pathophysiology of glucagon action and resistance.
• Findings could inform the development of glucagon-based therapeutic strategies.