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PDX1LOW MAFALOW β-cells contribute to islet function and insulin release
- Source :
- Nat. Commun. 12:674 (2021), Nature Communications, Nature Communications, Vol 12, Iss 1, Pp 1-19 (2021)
- Publication Year :
- 2021
- Publisher :
- Nature Portfolio, 2021.
-
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.<br />Beta cell subpopulations with low expression in PDX1, MAFA, and insulin might contribute to islet function and insulin release. Here the authors show that altering the proportion of PDX1LOW MAFALOW to PDX1HIGH MAFAHIGH cells impairs islet function.
- Subjects :
- 0301 basic medicine
endocrine system
endocrine system diseases
Science
Transgene
medicine.medical_treatment
Population
General Physics and Astronomy
030209 endocrinology & metabolism
Biology
General Biochemistry, Genetics and Molecular Biology
Article
Transcriptome
03 medical and health sciences
0302 clinical medicine
medicine
education
geography
education.field_of_study
Multidisciplinary
geography.geographical_feature_category
Insulin
Type 2 diabetes
General Chemistry
Islet
Cell biology
030104 developmental biology
Cell culture
PDX1
Function (biology)
Cell signalling
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Nat. Commun. 12:674 (2021), Nature Communications, Nature Communications, Vol 12, Iss 1, Pp 1-19 (2021)
- Accession number :
- edsair.doi.dedup.....fed6129b09188b234293ada2d9e691a2