Role of Alpha-to-beta Cell Communication to Adapt Insulin Secretion to Insulin Resistance.
Alpha to Beta Cell Communication in Health and Disease
Who can join
Ages 18 to 60 · All sexes · Healthy volunteers welcome
Full eligibility 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
About the study
Glucagon secretion from α-cells has long been viewed as primarily a counterregulatory mechanism - e.g. an agent with a role to prevent blood sugar from decreasing to levels that compromise function. Our group, along with other researchers, have begun to identify a much more complex role for α-cells, raising questions about when and how glucagon may influence blood glucose levels. This proposal looks to detail proglucagon peptide secretion from α-cells and the impact this has on β-cell function and glucose tolerance, in preclinical studies of human islets and translational studies in human subjects.
This protocol registration describes Aim 2 from this NIH grant which involves 2 study populations and separate protocols but addresses a common question. Aim 3 in the grant is focused on a separate hypothesis and will be conducted and published separately from Aim 2.
What is being tested
- Exendin-9 is a 30 amino acid peptide that is an established competitive antagonist of the GLP-1 receptor. Subjects will receive exendin-9 by intravenous infusion at a rate of 600 pmol/kg/min (drug)
- Dexamethasone (drug)
Sponsor: David D'Alessio, M.D. · Participants: 30 · Started: Dec 30, 2025
Contact the study team
- Johanna Johnson, MS · Phone: 919-660-6766
- Alyssa Sudnick, MS · Phone: 919-660-6769
Official record on ClinicalTrials.gov — NCT07224334
Locations in the U.S.
| North Carolina | Duke Center for Living, Durham |
Conditions
From ClinicalTrials.gov, data retrieved Sep 30, 2026. Each study sets its own eligibility; the study team decides who can join.