The Effect of Glucagon on Rates of Hepatic Mitochondrial Oxidation in Man Assessed by PINTA

• Status: Active, not recruiting
• Trial end date: 2023-12-06
• Target enrollment: 0
• Participant gender: All

Summary

It is well established that alterations in the portal vein insulin:glucagon ratio play a major role in the dysregulated hepatic glucose metabolism in type 2 diabetes but the molecular mechanism by which glucagon promotes alterations in hepatic glucose production and mitochondrial oxidation remain poorly understood. This is borne out of the fact that both glucagon agonists and antagonists are being developed to treat type 2 diabetes with unclear mechanisms of action.

This study will directly assess the effects of glucagon on rates of mitochondrial oxidation and pyruvate carboxylase flux for the first time in humans using PINTA analysis. The results will have important implications for the possibility of intervening in the pathogenesis of non alcoholic fatty liver and type 2 diabetes via chronic dual GLP-1/glucagon receptor antagonism and provide an important rationale for why a dual agonist may be more efficacious for treatment of non alcoholic fatty liver and T2D than GLP-1 alone.

• Phase: N/A
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Yale University
• Collaborators: Merck Sharp & Dohme Corp.; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Treatments: Glucagon; Glucagon-Like Peptide 1

Criteria

Inclusion Criteria:

• Healthy

• Normal body weight (BMI<28 Kg/m2)

• Non smoking

• Taking no medications except birth control

Exclusion Criteria:

• Any systemic or organ disease

• Smoking

• Taking any drug or medications other than birth control (women)