Integrated Pancreatic Blood Flow: Bidirectional Microcirculation Between Endocrine and Exocrine Pancreas

Dybala, Michael P.; Kuznetsov, Andrey V.; Motobu, Maki; Hendren-Santiago, Bryce; Philipson, Louis H.; Chervonsky, Alexander V.; Hara, Manami

doi:10.2337/db19-1034

Cited by 67 publications

(56 citation statements)

References 48 publications

(53 reference statements)

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“…Here we show that changes in the activity of islet pericytes and “SMC” pericytes mediate vasomotion in human islets and propose that these cells function as local gates. Given recent functional evidence in mice that the islet microcirculation is open and not isolated from that of the surrounding exocrine tissue ( 51 ), and the fact that in humans an islet-portal circulatory system is also well developed ( 41 ), the existence of such a gating system would allow islet blood flow to be regulated independently of the exocrine tissue under certain conditions, as previously suggested ( 52 ).…”

Section: Discussionmentioning

confidence: 91%

Functional Characterization of the Human Islet Microvasculature Using Living Pancreas Slices

Gonçalves

Almaça

2021

Front. Endocrinol.

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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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Section: Discussionmentioning

confidence: 91%

Functional Characterization of the Human Islet Microvasculature Using Living Pancreas Slices

Gonçalves

Almaça

2021

Front. Endocrinol.

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“…These studies suggested that a paracrine effect of glucagon on pancreatic beta cells in rodents is probably relatively minor. This view of rodent islet blood flow has long been under discussion (see [39] for the different models of islet microcirculation) and new observations utilising in vivo imaging of islet blood flow challenge even these models [40], making the issue of paracrine effects through the bloodstream for rodent islets open for debate. Another study arguing against the importance of a paracrine interaction between alpha and beta cells involved the generation of the glucagon-DTR mouse, a mouse that expressed the diphtheria toxin receptor (DTR) in pancreatic alpha cells.…”

Section: Is Glucagon a Paracrine Signal In Vivo?mentioning

confidence: 99%

Alpha cell regulation of beta cell function

2020

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The islet of Langerhans is a complex endocrine micro-organ consisting of a multitude of endocrine and non-endocrine cell types. The two most abundant and prominent endocrine cell types, the beta and the alpha cells, are essential for the maintenance of blood glucose homeostasis. While the beta cell produces insulin, the only blood glucose-lowering hormone of the body, the alpha cell releases glucagon, which elevates blood glucose. Under physiological conditions, these two cell types affect each other in a paracrine manner. While the release products of the beta cell inhibit alpha cell function, the alpha cell releases factors that are stimulatory for beta cell function and increase glucose-stimulated insulin secretion. The aim of this review is to provide a comprehensive overview of recent research into the regulation of beta cell function by alpha cells, focusing on the effect of alpha cell-secreted factors, such as glucagon and acetylcholine. The consequences of differences in islet architecture between species on the interplay between alpha and beta cells is also discussed. Finally, we give a perspective on the possibility of using an in vivo imaging approach to study the interactions between human alpha and beta cells under in vivo conditions.

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“…Islets, comprised of highly vascularised clusters of endocrine cells, are the functional units within the pancreas that control blood sugar levels. A dense capillary network surrounds and penetrates each pancreatic islet to enable glucose sensing and insulin secretion into peripheral circulation ( 5 – 8 ). While representing only 1–2% of the pancreatic mass, islets receive up to 20% of the direct arterial blood flow to the pancreas ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

The Role of Vascular Cells in Pancreatic Beta-Cell Function

et al. 2021

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Insulin-producing β-cells constitute the majority of the cells in the pancreatic islets. Dysfunction of these cells is a key factor in the loss of glucose regulation that characterizes type 2 diabetes. The regulation of many of the functions of β-cells relies on their close interaction with the intra-islet microvasculature, comprised of endothelial cells and pericytes. In addition to providing islet blood supply, cells of the islet vasculature directly regulate β-cell activity through the secretion of growth factors and other molecules. These factors come from capillary mural pericytes and endothelial cells, and have been shown to promote insulin gene expression, insulin secretion, and β-cell proliferation. This review focuses on the intimate crosstalk of the vascular cells and β-cells and its role in glucose homeostasis and diabetes.

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Integrated Pancreatic Blood Flow: Bidirectional Microcirculation Between Endocrine and Exocrine Pancreas

Cited by 67 publications

References 48 publications

Functional Characterization of the Human Islet Microvasculature Using Living Pancreas Slices

Functional Characterization of the Human Islet Microvasculature Using Living Pancreas Slices

Alpha cell regulation of beta cell function

The Role of Vascular Cells in Pancreatic Beta-Cell Function

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