Label-free light scattering monitors insulin granule dynamics and chromatin remodeling in live diabetic islets

Hundreds of millions worldwide suffer from type 2 diabetes (T2D) defined by chronically elevated blood glucose levels. A critical aspect of T2D is the dysfunction of pancreatic beta cells, which produce insulin and reside within pancreatic islets. However, the cellular events that drive beta cell failure remain unclear. To explore this, we use a light scattering–based microscopy method integrated with an islet-on-a-chip to monitor insulin granule modifications and chromatin remodeling in live, functional human islets from T2D donors. The approach is validated by label-free tracking glucose-stimulated insulin secretion and visualizing individual insulin granules in non-diabetic islets. By comparing diabetic and non-diabetic islets, we identify specific changes in granule structure and chromatin patterns associated with T2D. This label-free platform enables longitudinal tracking of β-cell changes in intact, functional human islets.