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

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.

Contrast-enhanced ultrasound measurement of pancreatic blood flow dynamics predicts type1 diabetes therapeutic reversal in preclinical models

“…We and others have previously demonstrated in models of T1D that changes to the pancreas blood flow reflect changes to islet-specific blood flow dynamics [10,21,22]. Islet blood flow dynamics also correlate with remodeling of the islet microvasculature that occurs in both mouse models of T1D and human T1D [7][8][9]23,24]. Altered microvascular organization may result from inflammation and thus lead to altered islet blood flow [7,25,26].…”

“…We previously demonstrated that contrast-enhanced ultrasound measurements of pancreas blood flow dynamics could reveal changes in islet blood flow dynamics that result from islet microvascular remodeling during T1D progression [7][8][9]. We demonstrated that these measurements could predict both the speed of diabetes progression and the success of interventions deigned to prevent T1D, using preclinical mouse models of T1D [10].…”

VEGF-A and blood vessels: a beta cell perspective

“…Both islet vascularisation and glucose tolerance were restored by increasing intra-islet VEGF-A levels through daily glucose injections for 14 days [44]. Finally, although few reports exist on the intra-islet vascular adaptations in the pancreas of patients with type 1 diabetes, islet vessels were recently shown to be smaller and more numerous than those observed in non-diabetic control individuals [45].…”

Exploration of NPTX2 in Islets of Langerhans

“…Images were taken at 20x magnification on a Zeiss 710 confocal microscope. A script was generated using ImageJ to calculate the Mander's correlation coefficient of NPTX2 co-localized with insulin and NPTX2 co-localized with glucagon based on previous reported methods (Canzano, et al, 2018). Using Mander's overlap coefficient equation, a value is obtained that identifies how much overlap of location exists between specific protein(s) and/or hormone (s) within an islet cell.…”