[HTML][HTML] PDX1LOW MAFALOW β-cells contribute to islet function and insulin release
Nature communications, 2021•nature.com
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
PDX1HIGH and MAFAHIGH β-cells reveals defects in metabolism, ionic fluxes and insulin
secretion. At the transcriptomic level, the presence of increased numbers of PDX1HIGH and …
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
PDX1HIGH and MAFAHIGH β-cells reveals defects in metabolism, ionic fluxes and insulin
secretion. At the transcriptomic level, the presence of increased numbers of PDX1HIGH and …
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 PDX1HIGH and MAFAHIGH β-cells reveals defects in metabolism, ionic fluxes and insulin secretion. At the transcriptomic level, the presence of increased numbers of PDX1HIGH and MAFAHIGH 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+ signaling patterns. During metabolic stress, islet function can be restored by redressing the balance between PDX1 and MAFA levels across the β-cell population. Thus, preserving heterogeneity in PDX1 and MAFA expression, and more widely in β-cell maturity, might be important for the maintenance of islet function.
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