Single‑cell transcriptomic profiling of human pancreatic islets reveals genes responsive to glucose exposure over 24 h – published online 05/07/2024

Caleb M. Grenko, Henry J. Taylor, Lori L. Bonnycastle, Dongxiang Xue, Brian N. Lee, Zoe Weiss, Tingfen Yan, Amy J. Swift, Erin C. Mansell, Angela Lee, Catherine C. Robertson, Narisu Narisu, Michael R. Erdos, Shuibing Chen, Francis S. Collins, D. Leland Taylor

Sustained hyperglycaemia, such as occurs in diabetes, is toxic to pancreatic islet beta cells and can lead to beta cell death. In this issue, Grenko, Taylor and Bonnycastle et al (https://doi.org/10.1007/s00125-024-06214-4) use single-cell RNA seq to profile >68,000 cells from islets exposed to low and high glucose for 24 h. They identify thousands of genes associated with time in culture, glucose exposure and time–glucose interaction effects and highlight that beta cells demonstrate unique association patterns across all three effects. Integrating genetic summary statistics, the authors nominate candidate effector genes and functionally characterise the effects of three genes on glucose-stimulated insulin production and secretion in a human beta cell line. The authors conclude that this study reveals transcriptional pathways activated by sustained hyperglycaemia in islet cells that may be relevant to diabetes pathogenesis.