Progenitor Cell Marker Aldehyde Dehydrogenase 1a3 Defines a Subset of Failing Pancreatic Beta Cells in Diabetic Mice

ABSTRACT: Insulin-producing beta cells become dedifferentiated during diabetes progression. An impaired ability to select substrates for oxidative phosphorylation, or metabolic inflexibility, sets the stage for progression from beta cell dysfunction to beta cell dedifferentiation. In this study, we sought to isolate and functionally characterize failing beta cells, as a preliminary step to identify pathways to reverse dedifferentiation. Using various experimental models of diabetes, we found a striking enrichment in the expression of aldehyde dehydrogenase 1 isoform A3 (ALDH+) as beta cells become dedifferentiated. Flow-sorted ALDH+ islet cells demonstrate impaired glucose-induced insulin secretion, are depleted of Foxo1 and MafA, and include a Neurogenin3-positive subset. RNA sequencing analysis de

ORGANISM(S): Mus musculus

SUBMITTER: Youngjung Kim 

PROVIDER: E-GEOD-78966 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress