How alpha‑cell signals change beta‑cell insulin release during insulin resistance
Alpha to Beta Cell Communication in Health and Disease
This project tests whether blocking GLP‑1 signaling changes how alpha‑cell hormones affect insulin release in non‑diabetic adults with and without obesity, before and after short‑term insulin resistance.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 30 (estimated) |
| Ages | 18 Years to 60 Years |
| Sex | All |
| Sponsor | Duke University Academic / other |
| Locations | 1 site (Durham, North Carolina) |
| Trial ID | NCT07224334 on ClinicalTrials.gov |
What this trial studies
Participants are screened for medical history, medications, and blood work and then complete one to two multi‑hour metabolic clamp visits depending on the study arm. In Aim 2A, lean adults undergo two 5‑hour hyperglycemic clamps with GLP‑1 receptor blockade (exendin‑9) before and after short‑term dexamethasone‑induced insulin resistance. In Aim 2B, adults with obesity undergo paired hyperglycemic clamps (with saline control and with exendin‑9) plus a hyperinsulinemic‑euglycemic clamp to measure insulin sensitivity. The primary measures are insulin secretion responses to glucose with and without GLP‑1 receptor blockade and changes in insulin sensitivity.
Who should consider this trial
Good fit: Non‑diabetic adults who meet the age, BMI, and glucose/A1c criteria for either arm (Aim 2A: ages 18–45, BMI <27 and normal glucose; Aim 2B: ages 35–60, BMI ≥27 and non‑diabetic) and who have no major medical conditions or interfering medications are ideal candidates.
Not a fit: People with diagnosed diabetes, pancreatitis, significant cardiac/renal/hepatic disease, pregnancy, poor venous access, or who take medications that alter glucose or gut function are excluded and unlikely to benefit from participation.
Why it matters
Potential benefit: If successful, the work could clarify how alpha‑cell peptides regulate beta‑cell insulin output and point to new targets for preventing or treating early metabolic dysfunction.
How similar studies have performed: Previous preclinical and human physiology studies using GLP‑1 receptor blockade and steroid‑induced insulin resistance have shown effects on insulin secretion, but combining exendin‑9 with paired hyperglycemic clamps before and after induced insulin resistance is a relatively novel translational approach.
Eligibility criteria
Show full inclusion / exclusion criteria
Aim 2A: Inclusion Criteria: * Age 18-45 * Body Mass Index (BMI) \< 27.0 * Fasting plasma glucose of ≤ 95 mg/dL or HbA1c value ≤ 5.8% as measured at screening visit Exclusion Criteria: * Active medical disease: e.g. active infectious, inflammatory, neurodegenerative or mental health disorders * Personal history of diabetes or pancreatitis * Personal history of cardiac, gastrointestinal, renal or liver disease * Immediate family history of diabetes * Renal insufficiency (eGFR \< 60 mL/kg/min) * Anemia (hematocrit \< 34%) as measured at screening visit * Pregnant females * Poor vein access * Consumption of daily medications that alter glucose metabolism of GI function (glucocorticoids, psychotropics, narcotics, metoclopramide) * Apparent sensitivity to the study peptide as determined by the skin test Aim 2B: Inclusion Criteria: * Age 35-60 * Body Mass Index (BMI) ≥ 27.0 * Fasting plasma glucose of \< 126 mg/dL or HbA1c value \< 6.5% as measured at screening visit Exclusion Criteria: * Active medical disease: e.g. active infectious, inflammatory, neurodegenerative or mental health disorders * Personal history of diabetes or pancreatitis * Personal history of cardiac, gastrointestinal, renal or liver disease * Immediate family history of diabetes * Renal insufficiency (eGFR \< 60 mL/kg/min) * AST and/or ALT levels \> 3x the upper limit of the normal range * Anemia (hematocrit \< 34%) as measured at screening visit * Pregnant females * Poor vein access * Consumption of daily medications that alter glucose metabolism of GI function (glucocorticoids, psychotropics, narcotics, metoclopramide) * Apparent sensitivity to the study peptide as determined by the skin test
Where this trial is running
Durham, North Carolina
- Duke Center for Living — Durham, North Carolina, United States (Recruiting)
Study contacts
- Principal investigator: David D'Alessio, MD — Duke University
- Study coordinator: Johanna Johnson, MS
- Email: johanna.johnson@duke.edu
- Phone: 919-660-6766
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.