A Dose-response Study Examining the Contribution of GLP-1 Receptor Signaling to Glucagon-stimulated Insulin Secretion

Healthy Clinical Trial

Official title:

A Dose-response Study Examining the Contribution of GLP-1 Receptor Signaling to Glucagon-stimulated Insulin Secretion

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04459338
• Other study ID #: 20-003995
• Secondary ID: 5R01DK126206-03
• Status: Completed
• Phase: Phase 3
• Start date: March 4, 2021
• Est. completion date: June 14, 2022

Study information

• Verified date: June 2023
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The GLP-1 receptor (GLP1R) gene is found on the beta cells of the pancreas. Its role is in the control of blood sugar level by enhancing insulin secretion from the pancreas after eating a meal. The purpose of this research study is to evaluate the role of GLP1R in the response to elevated glucagon concentrations.

Description:

Glucagon within the islet can signal the β-cell through GLP1R, and acts as an insulin secretagogue. This signaling is blocked by exendin-9,39. The relative importance of glucagon signaling through its cognate receptor or through GLP1R is unknown. Despite the lower affinity of GLP1R for glucagon, intra-islet concentrations of glucagon are sufficiently high to stimulate GLP1R. The other situation where this may occur is in response to pharmacologic doses of glucagon as used for β-cell function testing or raising peripheral glucagon concentrations above fasting values. The experiments proposed will characterize the role of GLP1R in glucagon's actions on the β-cell and the potential therapeutic role of dual (GLP-1R and glucagon receptor) agonists for the treatment of T2DM and obesity.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: June 14, 2022
• Est. primary completion date: June 14, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 25 Years to 65 Years

Eligibility

Inclusion Criteria:

• 20 weight-stable, non-diabetic subjects

Exclusion Criteria:

• Age < 25 or > 65 years (to avoid studying subjects who could have latent type 1 diabetes, or the effects of age extremes in subjects with normal or impaired fasting glucose).

• HbA1c =5.9%

• Use of glucose-lowering agents.

• For female subjects: positive pregnancy test at the time of enrollment or study

• History of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and vagotomy.

• Active systemic illness or malignancy.

• Symptomatic macrovascular or microvascular disease.

Related Conditions & MeSH terms

• Healthy

Intervention

Biological:
• Exendin-9,39
Exendin-9,39 is a competitive antagonist of GLP-1 actions at the GLP-1 receptor

Other:
• Saline
Placebo comparator

Locations

Country	Name	City	State
United States	Mayo Clinic in Rochester	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Adrian Vella	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Insulin Secretion Rate During Exendin-9,39 Infusion vs. Insulin Secretion Rate During Saline Infusion	This is the area under the curve for insulin secretion over the duration of the hyperglycemic clamp (0 to 300 minutes during the study in the Clinical Research Unit).	Area under the curve was quantified at the end of the Saline Study and at the end of the Exendin-9,39 study

External Links

•   Mayo Clinic Clinical Trials