Cycling alpha cells in regenerative drug-treated human pancreatic islets may serve as key beta cell progenitors
Year: 2024
Type: article
Abstract: Diabetes results from an inadequate number of insulin-producing human beta cells. There is currently no clinically available effective means to restore beta cell mass in millions of people with diabetes. Although the DYRK1A inhibitors, either alone or in combination with GLP-1 receptor agonists (GLP-1) or transforming growth factor β (TGF-β) superfamily inhibitors (LY), induce beta cell replication and increase beta cell mass, the precise mechanisms of action remain elusive. Here we perform single-cell RNA sequencing on human pancreatic islets treated with a DYRK1A inhibitor, either alone or with GLP-1 or LY. We identify cycling alpha cells as the most responsive cells to DYRK1A inhibition. Lineage trajectory analyses suggest that cycling alpha cells may serve as precursor cells that transdifferentiate into beta cells. Collectively, in addition to enhancing expression of beta cell phenotypic genes in beta cells, our findings suggest that regenerative drugs may be targeting cycling alpha cells in human islets.
Source: Cell Reports Medicine
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,460
Awards: G1193134389, G132765669, G1332970950, G1359611882, G1493670431, G1740429162, G30550971, G3194319764, G3358720692, G3881485945, G3912185369, G5537186586, G5582335657, Biological and Medicinal Chemistry Approaches to Human Beta Cell Regeneration, G6177305277, COVID and Translational Science supercomputer (CATS), G8583507304, G9000021867, G9000052772, G9000065207, G9000091667, G9000160732, G9000185558, G9000222624, NYR-Diabetes Research Center (NYR-DRC)
OpenAlex ID: W4404919479