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ISLET BIOLOGY

Probing α-cell dysfunction in type 2 diabetes mellitus

Nature Reviews Endocrinology volume 18, page 195 (2022)Cite this article

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In diabetes mellitus, the glucagon secretory function of pancreatic islet α-cells is dysregulated; however, the underlying mechanisms are unclear. A new study in Cell Metabolism combines patch-clamp electrophysiology with single-cell RNA sequencing (patch-seq) to study the connection between transcript expression profiles and cell function in pancreatic islets in type 2 diabetes mellitus (T2DM).

Patch-seq performed on human control α-cells at low and high concentrations of glucose showed that the mitochondrial electron transport chain is linked with exocytosis. Interestingly, immature α-cells showed poor responsiveness to glucose. Next, the researchers compiled single-cell RNA-sequencing and immunostaining data obtained from islet cells from 67 human donors (controls and those with T2DM) at three glucose concentrations. Of note, Na+ current properties of islet cells were found to correlate with transcriptomic markers of α-cell function. Using the compiled data, electrophysiological fingerprinting classifier models were developed using machine learning. This approach demonstrated a heterogeneous loss of functional identity in α-cells from donors with T2DM. Furthermore, a subset of α-cells was defined with impaired function and exocytosis, and increased expression of lineage and immaturity markers.

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References

Original article

  • Dai, X.-Q. et al. Heterogenous impairment of a cell function in type 2 diabetes is linked to cell maturation state. Cell Metab. 34, 256–268 (2022)

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Related article

  • Benninger, R. K. P. & Kravets, V. The physiological role of β-cell heterogeneity in pancreatic islet function. Nat. Rev. Endocrinol. 18, 9–22 (2022)

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  1. Nature Reviews Endocrinology http://www.nature.com/nrendo/

    Shimona Starling

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  1. Shimona Starling
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Correspondence to Shimona Starling.

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Starling, S. Probing α-cell dysfunction in type 2 diabetes mellitus. Nat Rev Endocrinol 18, 195 (2022). https://doi.org/10.1038/s41574-022-00650-1

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  • DOI: https://doi.org/10.1038/s41574-022-00650-1

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