Effect of Glucagon on Fasting Insulin Secretion and Glucose Metabolism in Subjects Without Type 2 Diabetes

Last updated: April 14, 2025
Sponsor: Mayo Clinic
Overall Status: Active - Recruiting

Phase

N/A

Condition

Diabetes And Hypertension

Diabetes Prevention

Treatment

Glucagon

Glucose

Clinical Study ID

NCT06424106
24-002639
  • Ages 25-65
  • All Genders
  • Accepts Healthy Volunteers

Study Summary

Fasting hyperglycemia contributes disproportionately to nonenzymatic glycosylation and the microvascular complications of type 2 diabetes. However, little is known about the regulation of glucose concentrations in the fasting state relative to what is known about the postprandial state. The proposed experiment is part of a series of experiments designed to establish how glucagon and insulin interact with their receptors to control fasting glucose in health and in prediabetes.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Individuals with normal or impaired fasting glucose and normal or impaired glucosetolerance

Exclusion

Exclusion Criteria:

  • HbA1c less than 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: Glucagon
Phase:
Study Start date:
April 01, 2025
Estimated Completion Date:
July 01, 2027

Study Description

The interaction between α-cell and β-cell function to regulate fasting glucose is incompletely understood. This is an important gap in our knowledge as fasting glucose contributes disproportionately to HbA1c and the microvascular complications of type 2 diabetes (T2DM). The regulation of fasting glucose in health and disease is relatively understudied.

Insulin and glucagon should regulate glucose reciprocally through direct interaction; insulin restrains α-cell secretion while glucagon directly stimulates β-cell secretion. In addition, there are indirect interactions via changes in glucose. Glucagon increases endogenous glucose production (EGP) increasing glucose (and insulin secretion). Conversely, insulin stimulates glucose disappearance (Rd) and suppresses EGP, lowering glucose (and stimulating glucagon).

However, this does not appear to occur uniformly in prediabetes. For example, in impaired fasting glucose (IFG), glucagon secretion rate (GSR) is inappropriate for the prevailing glucose. This is not accompanied by reciprocal changes in insulin secretion rate (ISR). Variability in the hepatic response to glucagon and to insulin further compound the dysregulation of fasting glucose. The net effect of these variables is unknown. This experiment is intended to test the hypothesis that impaired glucagon-induced insulin secretion contributes to fasting hyperglycemia in IFG.

Connect with a study center

  • Mayo Clinic in Rochester

    Rochester, Minnesota 55905
    United States

    Active - Recruiting

Map preview placeholder

Not the study for you?

Let us help you find the best match. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.