title: Human Islets Have Fewer Blood Vessels than Mouse Islets and the Density of Islet Vascular Structures Is Increased in Type 2 Diabetes.
abstract: Human and rodent islets differ substantially in several features, including architecture, cell composition, gene expression and some aspects of insulin secretion. Mouse pancreatic islets are highly vascularized with interactions between islet endothelial and endocrine cells being important for islet cell differentiation and function. To determine whether human islets have a similar high degree of vascularization and whether this is altered with diabetes, we examined the vascularization of islets from normal human subjects, subjects with type 2 diabetes (T2D), and normal mice. Using an integrated morphometry approach to quantify intra-islet capillary density in human and mouse pancreatic sections, we found that human islets have five-fold fewer vessels per islet area than mouse islets. Islets in pancreatic sections from T2D subjects showed capillary thickening, some capillary fragmentation and had increased vessel density as compared with non-diabetic controls. These changes in islet vasculature in T2D islets appeared to be associated with amyloid deposition, which was noted in islets from 8/9 T2D subjects (and occupied 14% ± 4% of islet area), especially around the intra-islet capillaries. The physiological implications of the differences in the angioarchitecture of mouse and human islets are not known. Islet vascular changes in T2D may exacerbate β cell/islet dysfunction and β cell loss.
authors.affiliation: Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University, Nashville Medical Center, Tennessee (MB, AS, ACP)
authors.forename: Marcela
authors.initials: M
authors.lastname: Brissova
authors.affiliation: Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University, Nashville Medical Center, Tennessee (MB, AS, ACP)
authors.forename: Alena
authors.initials: A
authors.lastname: Shostak
authors.affiliation: Department of Pathology, University of Washington, Seattle, Washington (CLF)
authors.forename: Corinne L
authors.initials: CL
authors.lastname: Fligner
authors.affiliation: Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee (FLR, MKW)
authors.forename: Frank L
authors.initials: FL
authors.lastname: Revetta
authors.affiliation: Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee (FLR, MKW)
authors.forename: Mary K
authors.initials: MK
authors.lastname: Washington
authors.affiliation: Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University, Nashville Medical Center, Tennessee (MB, AS, ACP)|Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee (ACP)|VA Tennessee Valley Healthcare System, Nashville, Tennessee (ACP)
authors.forename: Alvin C
authors.initials: AC
authors.lastname: Powers
authors.affiliation: Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee (FLR, MKW)|Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, VA Puget Sound Health Care System and University of Washington, Seattle, Washington (RLH)
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Hull
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000098:blood supply* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL
keywords: amyloid; diabetes; islet; pancreas; vasculature