T3 Induces Both Markers of Maturation and Aging in Pancreatic β-Cells.

ABSTRACT: Previously, we showed that thyroid hormone (TH) triiodothyronine (T3) enhanced β-cell functional maturation through induction of Mafa High levels of T3 have been linked to decreased life span in mammals and low levels to lengthened life span, suggesting a relationship between TH and aging. Here, we show that T3 increased p16Ink4a (a β-cell senescence marker and effector) mRNA in rodent and human β-cells. The kinetics of Mafa and p16Ink4a induction suggested both genes as targets of TH via TH receptors (THRs) binding to specific response elements. Using specific agonists CO23 and GC1, we showed that p16Ink4a expression was controlled by THRA and Mafa by THRB. Using chromatin immunoprecipitation and a transient transfection yielding biotinylated THRB1 or THRA isoforms to achieve specificity,

SUBMITTER: Aguayo-Mazzucato C 

PROVIDER: S-EPMC6014556 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature