T3 and glucose increase expression of phosphoenolpyruvate carboxykinase (PCK1) leading to increased β-cell proliferation.

ABSTRACT:

Objectives

Thyroid hormone (T3) and high glucose concentrations are critical components of β-cell maturation and function. In the present study, we asked whether T3 and glucose signaling pathways coordinately regulate transcription of genes important for β-cell function and proliferation.

Methods

RNA-seq analysis was performed on cadaveric human islets from five different donors in response to low and high glucose concentrations and in the presence or absence of T3. Gene expression was also studies in sorted human β-cells, mouse islets and Ins-1 cells by RT-qPCR. Silencing of the thyroid hormone receptors (THR) was conducted using lentiviruses. Proliferation was assessed by ki67 immunostaining in primary human/mouse islets. Chromatin immunoprecipitation and proximity ligatio

SUBMITTER: Katz LS 

PROVIDER: S-EPMC9731891 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature