Aldehyde dehydrogenase 1a3 defines a subset of failing pancreatic β cells in diabetic mice.

ABSTRACT: Insulin-producing β cells become dedifferentiated during diabetes progression. An impaired ability to select substrates for oxidative phosphorylation, or metabolic inflexibility, initiates progression from β-cell dysfunction to β-cell dedifferentiation. The identification of pathways involved in dedifferentiation may provide clues to its reversal. Here we isolate and functionally characterize failing β cells from various experimental models of diabetes and report a striking enrichment in the expression of aldehyde dehydrogenase 1 isoform A3 (ALDH(+)) as β 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 demonstrates that AL

SUBMITTER: Kim-Muller JY 

PROVIDER: S-EPMC5013715 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature