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:
Participant gender:
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
Details
Lead Sponsor:
Yale University
Collaborators:
Merck Sharp & Dohme Corp. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)