Role of Alpha-to-beta Cell Communication to Adapt Insulin Secretion to Insulin Resistance.

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.

NCT Number	NCT07224334
Lead Sponsor	David D'Alessio, M.D. Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Conditions	Diabetes (DM)
Enrollment	30 participants
Start Date	2025-12-30
Primary Completion	2027-12 (estimated)
Study Completion	2027-12 (estimated)
Updated on ClinicalTrials.gov	2026-02-05