The Effects of Glucagon on Hepatic Metabolism

NCT ID: NCT05500586

Last Updated: 2025-11-10

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-20
• Study Completion Date: 2026-03-31

Brief Summary

Whether impaired postprandial glucagon suppression in prediabetes and T2DM is an attempt to overcome resistance to glucagon's actions on hepatic AA catabolism, a defect in α-cell function, or a combination of both are important, unanswered questions. NAFLD is associated with T2DM risk and impaired insulin action. Unfortunately, it is unclear if glucagon resistance is caused by obesity, hepatic steatosis or both. The experiments outlined will determine if glucagon's actions on hepatic amino acid catabolism and EGP interact with hepatic lipid metabolism in lean and obese subjects with and without T2DM (and with varying degrees of hepatic steatosis).

Detailed Description

T2DM and prediabetes are characterized by abnormal post-prandial suppression of glucagon, which contributes to postprandial hyperglycemia by increasing EGP. Although these effects are magnified by decreased and delayed insulin secretion, they are also apparent when insulin secretion is intact. In rodents, altered glucagon signaling changes α-cell function and mass - an effect mediated by changes in circulating AA concentrations. Are the elevated concentrations of branched-chain AA and other AA metabolites in T2DM a cause or an effect of global α-cell dysfunction? Could altered glucagon signaling precipitate a vicious cycle resulting in T2DM?

Conditions

Obesity; Type2diabetes; NAFLD

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Healthy Adults

We will study 20 subjects on one occasion using a hyperglycemic clamp with 2 doses of glucagon.

Group Type: EXPERIMENTAL

Glucagon response study

Intervention Type: DRUG

Please see information in group descriptions

Obese Adults

We will study 20 subjects on one occasion using a hyperglycemic clamp with 2 doses of glucagon.

Group Type: EXPERIMENTAL

Glucagon response study

Intervention Type: DRUG

Please see information in group descriptions

Adults with Type 2 Diabetes

We will study 20 subjects on one occasion using a hyperglycemic clamp with 2 doses of glucagon.

Group Type: EXPERIMENTAL

Glucagon response study

Intervention Type: DRUG

Please see information in group descriptions

Interventions

Glucagon response study

Please see information in group descriptions

Intervention Type: DRUG

Other Intervention Names

Glucagon

Eligibility Criteria

Inclusion Criteria

• Willing to participate
• Able to give consent

Exclusion Criteria

• History of prior upper abdominal surgery e.g. gastric banding, pyloroplasty, vagotomy.
• Active systemic illness or malignancy.
• Symptomatic macrovascular or microvascular disease.
• Contraindications to MRI (e.g. metal implants, claustrophobia).
• Hematocrit < 35%
• TSH < 0.4 or > 5.5.
• Consumption of > 2 alcohol drinks per day or > 14 per week or a positive AUDIT questionnaire

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Adrian Vella

OTHER

Sponsor Role: lead

Responsible Party

Adrian Vella

Regulatory Sponsor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Adrian Vella

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Countries

United States

Related Links

https://www.mayo.edu/research/clinical-trials

Mayo Clinic Clinical Trials

Other Identifiers

22-000113

Identifier Type: -

Identifier Source: org_study_id