APA
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Dai, X., Camunas-Soler, J., Briant, L., dos Santos, T., Spigelman, A., Walker, E. M., … MacDonald, P. (2021). Heterogenous impairment of α-cell function in type 2 diabetes is linked to cell maturation state. BioRxiv.
Chicago/Turabian
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Dai, X., J. Camunas-Soler, L. Briant, Theodore dos Santos, A. Spigelman, Emily M. Walker, Rafael Arrojo e Drigo, et al. “Heterogenous Impairment of α-Cell Function in Type 2 Diabetes Is Linked to Cell Maturation State.” bioRxiv (2021).
MLA
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Dai, X., et al. “Heterogenous Impairment of α-Cell Function in Type 2 Diabetes Is Linked to Cell Maturation State.” BioRxiv, 2021.
BibTeX Click to copy
@article{x2021a,
title = {Heterogenous impairment of α-cell function in type 2 diabetes is linked to cell maturation state},
year = {2021},
journal = {bioRxiv},
author = {Dai, X. and Camunas-Soler, J. and Briant, L. and dos Santos, Theodore and Spigelman, A. and Walker, Emily M. and e Drigo, Rafael Arrojo and Bautista, Austin and Jones, Robert C. and Lyon, J. and Nie, Aifang and Smith, Nancy and Fox, J. M. and Kim, Seung K. and Rorsman, Patrik and Stein, Roland W and Quake, S. and MacDonald, P.}
}
In diabetes, glucagon secretion from pancreatic α-cells is dysregulated. We examined α-cells from human donors and mice using combined electrophysiological, transcriptomic, and computational approaches. Rising glucose suppresses α-cell exocytosis by reducing P/Q-type Ca2+ channel activity, and this is disrupted in type 2 diabetes (T2D). Upon high-fat-feeding of mice, α-cells shift towards a ‘β-cell-like’ electrophysiologic profile in concert with an up-regulation of the β-cell Na+ channel isoform Scn9a and indications of impaired α-cell identity. In human α-cells we identify links between cell membrane properties and cell surface signalling receptors, mitochondrial respiratory complex assembly, and cell maturation. Cell type classification using machine learning of electrophysiology data demonstrates a heterogenous loss of ‘electrophysiologic identity’ in α-cells from donors with T2D. Indeed, a sub-set of α-cells with impaired exocytosis is defined by an enrichment in progenitor markers suggesting important links between α-cell maturation state and dysfunction in T2D. Key findings α-cell exocytosis is suppressed by glucose-dependent inhibition of P/Q-type Ca2+ currents Dysfunction of α-cells in type 2 diabetes is associated with a ‘β-cell-like’ electrophysiologic signature Patch-seq links maturation state, the mitochondrial respiratory chain, and cell surface receptor expression to α-cell function α-cell dysfunction occurs preferentially in cells enriched in endocrine lineage markers