Endogenous GLP-1 Secretion on Islet Function in People With and Without Type 2 Diabetes

Healthy Clinical Trial

Official title:

To Determine the Effect of Endogenous GLP-1 Secretion on Islet Function in People With and Without Type 2 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04466618
• Other study ID #: 20-003993
• Secondary ID: R01DK126206
• Status: Completed
• Phase: Phase 3
• Start date: April 15, 2021
• Est. completion date: December 31, 2022

Study information

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

Clinical Trial Summary

GLP-1 is a hormone made by the body that promotes the production of insulin in response to GLP-1 is produced within the islets expressing prohormone convertase 1/3eating. However, there is increasing evidence that this hormone might help support the body's ability to produce insulin when diabetes develops. The purpose of this study is to determine the effect of endogenous GLP-1 secretion on insulin secretion in people with and without type 2 diabetes.

Description:

Accumulating evidence suggests that in rodents and humans GLP-1 is synthesized within islets and may act locally in a paracrine fashion. Indeed, mice with genetic loss of intra-islet GLP-1 exhibit decreased insulin secretion and impaired response to metabolic stressors. 'Pancreatic' GLP-1 may contribute to the effects of DPP-4 inhibitors in rodents and humans. Antagonism of GLP1R with exendin-9,39 during fasting impairs the islet cell response to an I.V. glucose challenge. Islet GLP-1 content is increased in T2DM and in islets from non-diabetic humans exposed to hyperglycemia and Free Fatty Acids. These observations imply that paracrine GLP-1 secretion supports islet function in the presence of glucolipotoxicity. In this experiment we will examine the role of endogenous GLP-1 secretion in people with and without T2DM and during β-cell stress induced by FFA elevation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: December 31, 2022
• Est. primary completion date: December 15, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 25 Years to 65 Years

Eligibility

Inclusion criteria - non-diabetic subjects:

• Weight-stable, non-diabetic subjects

Exclusion Criteria - non-diabetic subjects:

• 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 = 6.5%

• 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.

Inclusion criteria - diabetic subjects:

• Weight-stable, diabetic subjects treated with diet and lifestyle alone or with metformin monotherapy

Exclusion Criteria - diabetic subjects:

• 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).

• Use of any glucose-lowering agent other than metformin.

• 2 or more fasting glucose values > 250mg/dl on medication or after medication withdrawal.

• Unwillingness or inability to withdraw medication for three weeks prior to, and for the duration of the study.

• 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

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Healthy
• Type 2 Diabetes

Intervention

Biological:
• Saline
Saline infused during the study
• Exendin-9,39
Exendin-9,39 infused during the study
• Saline + Intralipid/Heparin
Saline infused during acute insulin resistance
• Exendin-9,39 + Intralipid/Heparin
Exendin-9,39 infused during acute insulin resistance

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	Change in Fasting Glucagon in the Presence or Absence of Exendin-9,39	Concentrations of glucagon Measured by immunoassay over the -30 to 0 minutes of study.; On one study day subjects received saline, on the other exendin-9,39. The infusion commenced at -120 minutes.	Average concentration over the -30 to 0 minutes of study

External Links

•   Mayo Clinic Clinical Trials