Abstract
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.
Highlights
Pancreatic islets are endocrine mini-organs rich in blood vessels [1, 2]
Pericytes can be identified in tissue sections using antibodies against pericyte surface markers, such as neuron-glial antigen 2 (NG2) and platelet-derived growth factor receptor-beta (PDGFRb)
To determine if pericytes in human islets help regulating islet capillary diameter, we examined in more detail pericytic expression of a-smooth muscle actin. aSMA is expressed by cells of smooth muscle cell lineages, allowing us to visualize arterioles that feed into pancreatic islets (Figures 1B, C)
Summary
Pancreatic islets are endocrine mini-organs rich in blood vessels [1, 2]. As any other endocrine organ, islets depend on their blood vessels to function properly [8]. Defects in the islet microvasculature can lead to diabetic phenotypes [9]. Several studies have reported structural alterations of the human islet microvasculature and composition of the extracellular matrix during type 1 and type 2 diabetes [10,11,12,13,14,15]. Microvascular dysfunction and abnormal regulation of islet blood flow could compromise exchanges between endocrine cells and the circulation, resulting in defective hormone secretion as previously suggested [18, 19]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
