ArticleDiabetes2024
Electrophysiological Characterization of Inducible Pluripotent Stem Cell-Derived Human β-Like Cells and an SLC30A8 Disease Model.
Article in Diabetes, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Postnatal refinement of CaChannels (Austin, Tex.) · 2026Article
- The comparative cell physiology of stem cell-derived and primary human β cells.Nature reviews. Endocrinology · 2026Review
- Pancreatic α cells are required for nutrient homeostasis by regulating dynamic β cell networks in islets.Science advances · 2026Article
- Extracellular electrophysiology on clonal human β-cell spheroids.Frontiers in endocrinology · 2024Article
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13 authors.
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Abstract
Inducible pluripotent stem cell-derived human β-like cells (BLCs) hold promise for both therapy and disease modeling, but their generation remains challenging and their functional analyses beyond transcriptomic and morphological assessments remain limited. Here, we validate an approach using multicellular and single-cell electrophysiological tools to evaluate function of BLCs from pioneer protocols that can be easily adapted to more differentiated BLCs. The multi-electrode arrays (MEAs) measuring the extracellular electrical activity revealed that BLCs, like primary β-cells, are electrically coupled and produce slow potential (SP) signals that are closely linked to insulin secretion. We also used high-resolution single-cell patch clamp measurements to capture the exocytotic properties, and characterize voltage-gated sodium and calcium currents, and found that they were comparable with those in primary β- and EndoC-βH1 cells. The KATP channel conductance is greater than in human primary β-cells, which may account for the limited glucose responsiveness observed with MEA. We used MEAs to study the impact of the type 2 diabetes-protective SLC30A8 allele (p.Lys34Serfs50*) and found that BLCs with this allele have stronger electrical coupling activity. Our data suggest that BLCs can be used to evaluate the functional impact of genetic variants on β-cell function and coupling. ARTICLE HIGHLIGHTS:
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