Islets of Langerhans articles from across Nature Portfolio

LSFM imaging revealed 3D islet maps: GADA+ cases mirrored controls, while short-duration T1D showed loss of small INS + GCG– islets but preserved larger mixed INS + GCG+ ones, highlighting islet size- and composition-dependent vulnerability

The pancreatic islets of Langerhans play a pivotal role in regulating blood glucose homeostasis through the regulated secretion of the hormones insulin and glucagon. Here, the authors use deep tissue 3D imaging to re-construct the entire human pancreas at microscopic resolution and display previously unrecognized heterogeneities in the islet’s cellularity with pre-clinical and clinical implications.

This study reveals functional heterogeneity at the level of exocytosis among β cells and identifies a subpopulation of β cells that make a disproportionally large contribution to insulin release from mouse islets.

Integration of multiomics data with functional analysis of pancreatic tissues from individuals with early-stage type 2 diabetes indicates that the genetic risk converges on RFX6, which regulates chromatin architecture at multiple risk loci.

Advances in islet cell biology over the past few years highlight a fundamental role for intra-islet endocrine cell interactions and δ-cells in the regulation of glycaemia. New insights into how cellular heterogeneity and individual-level heterogeneity effect hormone secretion have also emerged.