NCT06424015

Insulin and Insulin Pulses During Fasting

Effect of Insulin and Insulin Pulses on Fasting Glucagon Secretion and on 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

Decreased insulin action increases glucagon concentrations. In rodents, insulin signaling restrains glucagon secretion. It is unclear if this is the case in all (subtypes of) prediabetes. Impaired hepatic insulin action exacerbates glucagon's effects on endogenous glucose production. Also, insulin resistance in the β-cell impairs negative feedback inhibition of insulin secretion. This leads to hyperinsulinemia in rodents and humans. How these variables interact is unknown. This experiment will determine how insulin variably regulates fasting glucagon (and insulin) secretion directly, or indirectly, in prediabetes. The inability of the proinsulin to insulin ratio to reliably predict β-cell integrity, endoplasmic reticulum stress and β-cell function has led to the identification of novel markers of β-cell health. In addition, the relationship of glucagon and insulin pulses will be quantified. Preliminary data shows that there is heterogeneity in these relationships even in normal fasting glucose. Th experiment will also determine how islet hormone / glucose crosstalk and pulse characteristics contribute to prediabetes.

Conditions

• PreDiabetes

Interventions

Type	Name	Description
OTHER	Intralipid and heparin	Intralipid (20%, 0.011ml/kg/min; Baxter, Healthcare, Deerfield, IL) and heparin (200 units prime, 0.2 unit/kg/min continuous) will be infused to induce acute insulin resistance
OTHER	Saline	Saline will be infused

Timeline

• Start date: 2024-09-15
• Primary completion: 2026-09-01
• Completion: 2027-09-01
• First posted: 2024-05-21
• Last updated: 2025-10-01

Locations

1 site across 1 country: United States