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Functional Characterization of the Human Islet Microvasculature Using Living Pancreas Slices

Pancreatic islets are clusters of endocrine cells that secrete different hormones to regulate blood glucose levels. Efficient hormone secretion requires a close interaction of endocrine cells with their vascular system. Islets receive blood through feeding arteriole(s) that branch into capillaries m...

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Autores principales: Mateus Gonçalves, Luciana, Almaça, Joana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843926/
https://www.ncbi.nlm.nih.gov/pubmed/33519711
http://dx.doi.org/10.3389/fendo.2020.602519
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author Mateus Gonçalves, Luciana
Almaça, Joana
author_facet Mateus Gonçalves, Luciana
Almaça, Joana
author_sort Mateus Gonçalves, Luciana
collection PubMed
description Pancreatic islets are clusters of endocrine cells that secrete different hormones to regulate blood glucose levels. Efficient hormone secretion requires a close interaction of endocrine cells with their vascular system. Islets receive blood through feeding arteriole(s) that branch into capillaries made of endothelial cells covered by pericytes. While a lot is known about rodent islet blood vessels, the structure and function of the human islet microvasculature has been less investigated. In this study, we used living pancreas slices from non-diabetic human donors to examine the function of human islet blood vessels. Living human pancreas slices were incubated with a membrane permeant calcium indicator and pericytes/smooth muscle cells were visualized with a fluorescent antibody against the mural cell marker NG2 proteoglycan. By confocal microscopy, we simultaneously recorded changes in the diameter of lectin-labeled blood vessels and cytosolic calcium levels in mural cells in islets. We tested several stimuli with vasoactive properties, such as norepinephrine, endothelin-1 and adenosine and compared human vascular responses with those previously published for mouse islet blood vessels. Norepinephrine and endothelin-1 significantly constricted human islet feeding arterioles, while adenosine dilated them. Islet capillaries were less responsive and only 15–20% of the mouse and human islet capillary network showed vasomotion. Nevertheless, in these responsive regions, norepinephrine and endothelin-1 decreased both mouse and human islet capillary diameter. Changes in islet blood vessel diameter were coupled to changes in cytosolic calcium levels in adjacent mouse and human islet mural cells. Our study shows that mural cells in islets are the targets of different regulatory mechanisms of islet blood perfusion. Several alterations of the human islet microvasculature occur during diabetes progression. Elucidating their functional consequences in future studies will be critical for our understanding of disease pathogenesis.
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spelling pubmed-78439262021-01-30 Functional Characterization of the Human Islet Microvasculature Using Living Pancreas Slices Mateus Gonçalves, Luciana Almaça, Joana Front Endocrinol (Lausanne) Endocrinology Pancreatic islets are clusters of endocrine cells that secrete different hormones to regulate blood glucose levels. Efficient hormone secretion requires a close interaction of endocrine cells with their vascular system. Islets receive blood through feeding arteriole(s) that branch into capillaries made of endothelial cells covered by pericytes. While a lot is known about rodent islet blood vessels, the structure and function of the human islet microvasculature has been less investigated. In this study, we used living pancreas slices from non-diabetic human donors to examine the function of human islet blood vessels. Living human pancreas slices were incubated with a membrane permeant calcium indicator and pericytes/smooth muscle cells were visualized with a fluorescent antibody against the mural cell marker NG2 proteoglycan. By confocal microscopy, we simultaneously recorded changes in the diameter of lectin-labeled blood vessels and cytosolic calcium levels in mural cells in islets. We tested several stimuli with vasoactive properties, such as norepinephrine, endothelin-1 and adenosine and compared human vascular responses with those previously published for mouse islet blood vessels. Norepinephrine and endothelin-1 significantly constricted human islet feeding arterioles, while adenosine dilated them. Islet capillaries were less responsive and only 15–20% of the mouse and human islet capillary network showed vasomotion. Nevertheless, in these responsive regions, norepinephrine and endothelin-1 decreased both mouse and human islet capillary diameter. Changes in islet blood vessel diameter were coupled to changes in cytosolic calcium levels in adjacent mouse and human islet mural cells. Our study shows that mural cells in islets are the targets of different regulatory mechanisms of islet blood perfusion. Several alterations of the human islet microvasculature occur during diabetes progression. Elucidating their functional consequences in future studies will be critical for our understanding of disease pathogenesis. Frontiers Media S.A. 2021-01-15 /pmc/articles/PMC7843926/ /pubmed/33519711 http://dx.doi.org/10.3389/fendo.2020.602519 Text en Copyright © 2021 Mateus Gonçalves and Almaça http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Mateus Gonçalves, Luciana
Almaça, Joana
Functional Characterization of the Human Islet Microvasculature Using Living Pancreas Slices
title Functional Characterization of the Human Islet Microvasculature Using Living Pancreas Slices
title_full Functional Characterization of the Human Islet Microvasculature Using Living Pancreas Slices
title_fullStr Functional Characterization of the Human Islet Microvasculature Using Living Pancreas Slices
title_full_unstemmed Functional Characterization of the Human Islet Microvasculature Using Living Pancreas Slices
title_short Functional Characterization of the Human Islet Microvasculature Using Living Pancreas Slices
title_sort functional characterization of the human islet microvasculature using living pancreas slices
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843926/
https://www.ncbi.nlm.nih.gov/pubmed/33519711
http://dx.doi.org/10.3389/fendo.2020.602519
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