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

What Was Tested

In this phase 1 trial, researchers set out to test Glucagon.

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 rates of mitochondrial oxidation and pyruvate carboxylase flux for the first time in humans using PINTA analysis as well as the effects of glucagon.

It had two arms (groups): Glucagon (experimental) and Control (experimental).

Participants will receive glucagon during the PINTA study.

The same participants will not receive glucagon during the PINTA study.

The registry classes the interventions as biological and other.

More on the Plan

Briefly rates of hepatic mitochondrial oxidation and hepatic pyruvate carboxylase flux will be assessed in 12 healthy overnight fasted participants by PINTA after a three-hour infusion of glucagon or saline.

Briefly, after collection of baseline blood samples a 3 hour infusion of tracers as described below will be started.

Relative rates of pyruvate carboxylase to citrate synthesis flux will be assessed using a constant infusion of \[3-13C\] lactate and rates of glucose production will be measured using an infusion of \[2H7\]glucose (Perry et al.

Rates of hepatic ketogenesis will be measured using a constant infusion of \[3C β-hydroxybutyrate as previously described (Perry et al.

Who Took Part

Enrollment: 10 actual participants took part.

It was open to people of any sex aged from 21 years up to 65 years.

Healthy volunteers could join, not only people with the condition.

Examples of who could join: Taking no medications except birth control.

The full record lists 3 inclusion and 3 exclusion criteria; among the exclusions: any systemic or organ disease; taking any drug or medications other than birth control (women).

How the Study Was Run

Design: randomized, crossover and open-label.

Because people in this Glucagon study were split into groups at random, differences between the groups are less likely to reflect who happened to join each one.

Each person switched between Glucagon and the comparison at some point, usually with a gap in between.

Nothing was hidden in this open-label Glucagon study: the participants and staff both knew the treatment.

It started in 2019-06-05 with completion listed for 2022-07-07.

It ran at 1 site in United States.

Its stated primary purpose is basic science.

What Was Measured

Primary outcome: Rates of Hepatic Mitochondrial Oxidation (time frame: 5 hours).

What This Means in Plain Language

Put simply, this is a phase 1, randomized trial of Glucagon in 10 people.

Its size is small, so on its own it can only give an early look.

The trial is marked completed; results are posted on the registry, and this page does not restate them.

More context: the Glucagon compound page, all human trials.