Islet Microvasculature Alterations With Loss of Beta-cells in Patients With Type 1 Diabetes

J Histochem Cytochem. 2019 Jan;67(1):41-52. doi: 10.1369/0022155418778546. Epub 2018 May 17.

Abstract

Islet microvasculature provides key architectural and functional roles, yet the morphological features of islets from patients with type 1 diabetes are poorly defined. We examined islet and exocrine microvasculature networks by multiplex immunofluorescence imaging of pancreases from organ donors with and without type 1 diabetes (n=17 and n=16, respectively) and determined vessel diameter, density, and area. We also analyzed these variables in insulin-positive and insulin-negative islets of 7 type 1 diabetes donors. Control islet vessel diameter was significantly larger (7.6 ± 1.1 μm) compared with vessels in diabetic islets (6.2 ± 0.8 μm; p<0.001). Control islet vessel density (number/islet) was significantly lower (5.3 ± 0.6) versus diabetic islets (9.3 ± 0.2; p<0.001). Exocrine vessel variables were not significantly different between groups. Islets with residual beta-cells were comparable to control islets for both vessel diameter and density and were significantly different from insulin-negative islets within diabetic donors (p<0.05). Islet smooth muscle actin area had a significant positive correlation with age in both groups (p<0.05), which could negatively impact islet transplantation efficiency from older donors. These data underscore the critical relationship of islet beta-cells and islet vessel morphology in type 1 diabetes. These studies provide new knowledge of the islet microvasculature in diabetes and aging.

Keywords: CD3; CD31; CD34; alpha-cell; endothelium; exocrine; glucagon; insulin; microenvironment; secretogranin 3; smooth muscle actin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / analysis
  • Adolescent
  • Adult
  • Child
  • Diabetes Mellitus, Type 1 / pathology*
  • Female
  • Fluorescent Antibody Technique / methods
  • Humans
  • Insulin / analysis
  • Insulin-Secreting Cells / pathology*
  • Insulin-Secreting Cells / ultrastructure
  • Islets of Langerhans / blood supply
  • Islets of Langerhans / pathology
  • Islets of Langerhans / ultrastructure
  • Male
  • Microscopy, Confocal / methods
  • Microvessels / pathology*
  • Microvessels / ultrastructure
  • Tissue Donors
  • Young Adult

Substances

  • ACTA2 protein, human
  • Actins
  • Insulin