Ultra-structural study of insulin granules in pancreaticβ-cells of db/db mouse by scanning transmission electron microscopy tomography

Insulin granule trafficking is a key step in the secretion of glucose-stimulated insulin from pancreaticβ-cells.The main feature of type 2 diabetes(T2D)is the failure of pancreaticβ-cells to secrete sufficient amounts of insulin to maintain normal blood glucose levels.In this work,we developed and applied tomography based on scanning transmission electron microscopy(STEM)to image intact insulin granules in theβ-cells of mouse pancreatic islets.Using three-dimensional(3D)recon-struction,we found decreases in both the number and the grey level of insulin granules in db/db mouse pan-creaticβ-cells.Moreover,insulin granules were closer to the plasma membrane in diabeticβ-cells than in control cells.Thus,3D ultra-structural tomography may provide new insights into the pathology of insulin se-cretion in T2D.