Role of Alpha-to-beta Cell Communication to Adapt Insulin Secretion to Insulin Resistance.
Alpha to Beta Cell Communication in Health and Disease
David D'Alessio, M.D.
30 participants
Dec 30, 2025
INTERVENTIONAL
Conditions
Summary
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.
Eligibility
Inclusion Criteria6
- 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
- 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 Criteria21
- 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
- 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
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Interventions
Subjects in Aim 2A will receive exendin-9 on both experimental days and dexamethasone for one week before their second experimental day. Subjects in Aim 2B will receive exendin-9 on one of their two experimental days.
Dexamethasone 6 mg daily
Locations(1)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT07224334