Transcriptional and functional profiling reveals a dynamic continuum of beta-cell activation states.

Beta-cells show a sequential, spatially organized recruitment across increasing glucose, with high-threshold cells mainly in the islet core and activation marked by phospho-S6.

• Why it matters: It remains unclear whether beta-cells respond uniformly to glucose; defining how activation and function vary is key to understanding glucose homeostasis.
• What they did: Using phospho-S6 as an activation marker, the study profiled beta-cell activation and performed single-cell RNA sequencing to map transcriptomic functional subsets.
• The result: Functional subsets form a continuous spectrum, and under high-fat diet–induced metabolic demand islets remodel with globally reduced activation thresholds and a shift toward high-capacity profiles.

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