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

Phase 3

Completed

• Conditions: Healthy; Type 2 Diabetes

• Registration Number: NCT04466618
• Lead Sponsor: Adrian Vella

Brief 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.

Detailed 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.

Study Timeline

• Study First Submitted: 2020-06-30
• Study First Submitted QC: 2020-07-07
• Study First Posted: 2020-07-10
• Study Start: 2021-04-15
• Primary Completion: 2022-12-15
• Study Completion: 2022-12-31
• Results First Submitted: 2023-11-03
• Status Verified: 2023-12
• Results First Submitted QC: 2023-12-07
• Last Update Submitted: 2023-12-07
• Results First Posted: 2023-12-26
• Last Update Posted: 2023-12-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 23

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Change in Fasting Glucagon in the Presence or Absence of Exendin-9,39	Average concentration over the -30 to 0 minutes of study	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.

Trial Locations

Locations (1)

Mayo Clinic in Rochester; 🇺🇸 Rochester, Minnesota, United States