The Effects of Glucagon on Hepatic Metabolism

Sponsor

Adrian Vella (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05500586

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

2.2

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Obesity Type2diabetes NAFLD	Drug: Glucagon response study	Phase 1/Phase 2

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?

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

All subjects will undergo one study designed to measure the hepatic response to glucagon. There will be 3 groups non-diabetic and non-obese, obese, people with type 2 diabetesAll subjects will undergo one study designed to measure the hepatic response to glucagon. There will be 3 groups non-diabetic and non-obese, obese, people with type 2 diabetes

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

The Effects of Glucagon on Hepatic Metabolism

Anticipated Study Start Date :

Oct 1, 2022

Anticipated Primary Completion Date :

Sep 30, 2024

Anticipated Study Completion Date :

Dec 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Healthy Adults We will study 20 subjects on one occasion using a hyperglycemic clamp with 2 doses of glucagon.	Drug: Glucagon response study Please see information in group descriptions
Experimental: Obese Adults We will study 20 subjects on one occasion using a hyperglycemic clamp with 2 doses of glucagon.	Drug: Glucagon response study Please see information in group descriptions
Experimental: Adults with Type 2 Diabetes We will study 20 subjects on one occasion using a hyperglycemic clamp with 2 doses of glucagon.	Drug: Glucagon response study Please see information in group descriptions

Arm

Intervention/Treatment

Experimental: Healthy Adults

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

Drug: Glucagon response study

Please see information in group descriptions

Experimental: Obese Adults

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

Drug: Glucagon response study

Please see information in group descriptions

Experimental: Adults with Type 2 Diabetes

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

Drug: Glucagon response study

Please see information in group descriptions

Outcome Measures

Primary Outcome Measures

Rate of Amino acid catabolism in the presence / absence of glucagon [240 minutes of study]
Tracer-dependent measurement of amino-acid clearance

Secondary Outcome Measures

Effect of Diabetes on amino-acid catabolism [240 minutes of study]
Tracer-dependent measurement of amino-acid clearance

Eligibility Criteria

Criteria

Ages Eligible for Study:

25 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic in Rochester	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

Adrian Vella

Investigators

Principal Investigator: Adrian Vella, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Mayo Clinic Clinical Trials

Publications

None provided.

Responsible Party:

Adrian Vella, Regulatory Sponsor, Mayo Clinic

ClinicalTrials.gov Identifier:

NCT05500586

Other Study ID Numbers:

22-000113

First Posted:

Aug 15, 2022

Last Update Posted:

Aug 15, 2022

Last Verified:

Aug 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Adrian Vella, Regulatory Sponsor, Mayo Clinic

glucagon

insulin resistance

hepatic steatosis

amino acid metabolism

Additional relevant MeSH terms:

Glucagon

Study Results

No Results Posted as of Aug 15, 2022