FIG. 5.

ECM of human healthy and type 1 diabetic pancreata. A: Immunofluorescence staining reveals the BM component laminin (LM) α5 surrounding the insulin and glucagon-containing islet. Glucagon⁺ cells are organized along the peri-islet BM, whereas the insulin⁺ β-cells fill the inner part of the islet. B: Double-staining for pan-laminin (PLM) and other BM components, such as perlecan, show some colocalization in the peri-islet BM (arrow) and in the endothelial BM (arrowhead). C: The peri-islet BM is further surrounded by a dense network of IM, represented here by collagen type III. (A–C, nPOD case 6024, healthy pancreas) D: Schematic representation of the areas analyzed. In a recently diagnosed individual with type 1 diabetes (nPOD case 6052), insulin⁺/CD45⁺ islets were detected only in the pancreatic tail (E and F) but not in the head (G) of the pancreas, where only insulin⁻ (G) and glucagon⁺ (H) islets with intact BMs were present. The peri-islet BM is intact at sites where the leukocytes accumulate around the insulin⁺ islets (arrows in E) and is lost at sites of leukocyte invasion (arrowheads in E and F). H: Glucagon-producing α-cells become evenly distributed throughout the islet in type 1 diabetic CD45⁻/insulin⁻ samples and are enclosed within an intact peri-islet BM, as shown by laminin α5 staining. I and J: Staining of samples from individuals with recently diagnosed human type 1 diabetes show loss of the peri-islet BM at the front of the CD45⁺ cell infiltration (arrows) and colocalization of immunoreactivity for cathepsin S (I) and for cathepsin W (J). The peri-islet BM is marked here by perlecan staining. The boxed areas are shown at higher magnifications to the right. Scale bars are 100 μm. (A high-quality digital representation of this figure is available in the online issue.)