PDX1^LOW MAFA^LOW β-cells contribute to islet function and insulin release.

ABSTRACT: Transcriptionally mature and immature β-cells co-exist within the adult islet. How such diversity contributes to insulin release remains poorly understood. Here we show that subtle differences in β-cell maturity, defined using PDX1 and MAFA expression, contribute to islet operation. Functional mapping of rodent and human islets containing proportionally more PDX1^HIGH and MAFA^HIGH β-cells reveals defects in metabolism, ionic fluxes and insulin secretion. At the transcriptomic level, the presence of increased numbers of PDX1^HIGH and MAFA^HIGH β-cells leads to dysregulation of gene pathways involved in metabolic processes. Using a chemogenetic disruption strategy, differences in PDX1 and MAFA expression are shown to depend on islet Ca²⁺ si

SUBMITTER: Nasteska D 

PROVIDER: S-EPMC7846747 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature