Human islets are less vascularized than mouse islets. A–F: representative immunofluorescent staining (A and A′, B and B′) and quantification (C–F) of vasculature as measured by endothelial cell staining [platelet endothelial cell adhesion molecule 1 (PECAM-1) or caveolin-1 (CAV1); magenta]. Islets are visualized by hormones [insulin (INS), glucagon (GCG); green], and A′ and B′ show PECAM-1 or CAV1 only with islet area outlined. Scale bars, 100 μm. Quantification (mean ± SE) includes capillary density (C and D) and area per capillary in islets (E) and acinar tissue (F) from mouse (gray; N = 5 mice; 129 total islets, 127 total acinar measurements) and human (dark blue; N = 11 donors; 488 total islets, 1,392 total acinar measurements). Symbols on bar graphs represent individual mouse or human donors. Statistically significant P values (<0.05) are stated for Mann–Whitney tests. G and H: transcript levels of select angiogenic factors and receptors (G) and extracellular matrix (ECM) molecules (H) detected in islet endocrine cells, endothelial cells, and immune cells as measured by RNA sequencing (RNA-seq). From top to bottom: mouse bulk data sets (34); human bulk beta (β) (37); human bulk endothelial (EC) (36); single-cell (sc) data sets: mouse (38) and human (39). Boxed “M” and “H” label mouse and human data sets, respectively. Only values > 0.2 (sc) and log2 > 8 (bulk) are graphed. Normalized expression (NE) units vary by study; see research design and methods. Imm., immune; Stell., stellate; VEGF, vascular endothelial growth factor.