NCT06424106

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

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: Mayo Clinic · Academic / Other
• Sex: All
• Age: 25 Years – 65 Years
• Healthy volunteers: Accepted

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.

Detailed 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.

Conditions

• PreDiabetes

Interventions

Type	Name	Description
OTHER	Glucagon	a variable rate glucagon infusion
OTHER	Glucose	a variable rate glucose infusion

Timeline

• Start date: 2025-04-01
• Primary completion: 2027-07-01
• Completion: 2027-07-01
• First posted: 2024-05-21
• Last updated: 2025-04-15

Locations

1 site across 1 country: United States