The Role of Islet GLP-1 in the Pathogenesis of Prediabetes

Last updated: October 10, 2025
Sponsor: Mayo Clinic
Overall Status: Active - Not Recruiting

Phase

2

Condition

Diabetes And Hypertension

Diabetes Mellitus, Type 2

Diabetes Mellitus Types I And Ii

Treatment

Exendin 9-39

Saline

Clinical Study ID

NCT06967558
24-007677
  • Ages 25-70
  • All Genders
  • Accepts Healthy Volunteers

Study Summary

We recently demonstrated that blockade of Glucagon-Like Peptide-1's (GLP-1) receptor (GLP1R) results in changes in islet function without changes in circulating GLP-1. These effects are more pronounced in people with early type 2 diabetes (T2DM) in keeping with increased expression of PC-1/3 and GLP-1 that is observed in diabetic islets. However, its regulation is at present unknown. At present it is unknown if these abnormalities develop in prediabetes and whether they contribute to the phenotypes observed. In this experiment we will use blockade of GLP1R to probe the contribution of endogenous GLP-1 secretion to the regulation of fasting glucose and islet function in prediabetes.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • People with stable weight and no history of diabetes.

  • Fasting glucose < 126 mg/dL

  • 2hr glucose after 75g OGTT < 200 mg/dL

Exclusion

Exclusion Criteria:

  • Age < 25 or > 70 years (to avoid studying subjects who could have latent type 1diabetes, or the effects of age extremes in subjects with normal or impaired fastingglucose).

  • HbA1c > 6.5%

  • Use of any glucose-lowering agents including metformin or sulfonylureas.

  • 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.

Study Design

Total Participants: 60
Treatment Group(s): 2
Primary Treatment: Exendin 9-39
Phase: 2
Study Start date:
November 01, 2025
Estimated Completion Date:
March 31, 2028

Study Description

We recently demonstrated that blockade of Glucagon-Like Peptide-1's (GLP-1) receptor (GLP1R) results in changes in islet function without changes in circulating GLP-1. This supports other evidence (rodents and humans) that through the (inducible) expression of a prohormone convertase (PC-1/3), the α-cell can process proglucagon to intact GLP-1. 'Islet' or 'pancreatic' GLP-1 acts in a paracrine fashion to regulate insulin and glucagon secretion. These effects are more pronounced in people with early type 2 diabetes (T2DM). Although pancreatic GLP-1 adapts to support islet function in T2DM, it is unclear if this mechanism is upregulated in prediabetes and whether it contributes to the phenotype(s) observed. Abnormal α-cell responsivity to glucose, measured using G50, is associated with Impaired Fasting Glucose (IFG); β-cell dysfunction is associated with Impaired Glucose Tolerance (IGT). Does IGT (or IFG) represent selective failure of intra-islet GLP-1 to support islet function? In this experiment we will use blockade of GLP1R to probe the contribution of endogenous GLP-1 secretion to the regulation of fasting glucose and islet function in prediabetes

Connect with a study center

  • Mayo Clinic in Rochester

    Rochester, Minnesota 55905
    United States

    Site Not Available

  • Mayo Clinic in Rochester

    Rochester 5043473, Minnesota 5037779 55905
    United States

    Site Not Available

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