Blood vessels of human islets of Langerhans are surrounded by a double basement membrane

Abstract

Aims/hypothesis Based on mouse study findings, pancreatic islet cells are supposed to lack basement membrane (BM) and interact directly with vascular endothelial BM. Until now, the BM composition of human islets has remained elusive. Methods Immunohistochemistry with specific monoclonal and polyclonal antibodies as well as electron microscopy were used to study BM organisation and composition in human adult islets. Isolated islet cells and function-blocking monoclonal antibodies and recombinant soluble Lutheran peptide were further used to study islet cell adhesion to laminin (Lm)-511. Short-term cultures of islets were used to study Lutheran and integrin distribution. Results Immunohistochemistry revealed a unique organisation for human Lm-511/521 as a peri-islet BM, which coinvaginated into islets with vessels, forming an outer endocrine BM of the intra-islet vascular channels, and was distinct from the vascular BM that additionally contained Lm-411/421. These findings were verified by electron microscopy. Lutheran glycoprotein, a receptor for the Lm α5 chain, was found prominently on endocrine cells, as identified by immunohistochemistry and RT-PCR,

Superior beta cell proliferation, function and gene expression in a subpopulation of rat islets identified by high blood perfusion

“…All values are given as means±SEM from five to six experiments in each group. *p<0.05 compared with non-microsphere-containing islets beta2 chain of laminin has been shown to be prominent in vascular basement membranes in human islets also [25]. Upregulation of the clock components Arntl and Clock in higher blood-perfused islets may also contribute to their higher rate of beta cell proliferation (compare with the study of Marcheva et al [26]), although these genes were not upregulated in ECCM-exposed islets.…”

Endothelial cell signalling supports pancreatic beta cell function in the rat

“…In addition, the peri-islet capsule seems to be composed of LM chains α2, β1 and γ1, suggesting the presence of LM-211 [30]. At least in humans, LM-421 and LM-521 also seem to be present in the islet basement membranes [31].…”

An Apparent Deficiency of Lymphatic Capillaries in the Islets of Langerhans in the Human Pancreas

“…The few lymphatic capillaries identified within the islets were in most cases not in direct contact with the endocrine cells; instead, the capillaries detected were found in conjunction with fibrotic strands entering the islets. Lymphatic capillaries were instead often found in the peri-islet area, close to the blood vessels supporting the islet (i.e., the site into which a tentative glymphatic transport system would empty) (14). The importance of this observation for the development of T1D is unknown and beyond the scope of this study.…”

“…Notably, there are marked similarities in the morphological structure of the blood capillaries in the central nervous system and in human pancreatic islets, with a unique paravascular space surrounded by a double basal membrane structure (13,14). This peculiar anatomical structure, which functions as the prevailing transport system for EIF, has been described in the central nervous system (13,15,16).…”

“…Disturbances in the glymphatic pathway have been associated with accumulation of metabolic degradation products and the development of neurodegenerative diseases (15,16). Even if a similar paravascular space surrounded by a double basal membrane is present in human islets (14), no report thus far has described glymphatic transport of interstitial fluids and waste products in human islets.…”