The Pericyte of the Pancreatic Islet Regulates Capillary Diameter and Local Blood Flow

Almaça, Joana; Weitz, Jonathan; Rodriguez-Diaz, Rayner; Pereira, Elizabeth; Caicedo, Alejandro

doi:10.1016/j.cmet.2018.02.016

Cited by 152 publications

(205 citation statements)

References 82 publications

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“…It is also possible that not all pericytes have the capacity to respond to vasoactive agents. For instance only a subset of pericytes have been observed to express smooth muscle actin (αSMA) in the brain (Bandopadhyay et al, 2001), spinal cord (Roufail et al, 1995), retina (Nehls, 2004), and pancreatic islets (Almaça et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Development of vascular myogenic responses in zebrafish

Bahrami

Childs

2019

Preprint

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The vascular system is placed under enormous stress at the onset of cardiac contractility and blood flow. Nascent blood vessel tubes initially consist of a thin endothelial wall and rapidly acquire support from mural cells (pericytes and vascular smooth muscle cells; vSMCs). Following their association with vessels, mural cells acquire vasoactive ability (contraction and relaxation). However, we have little information as to when this vasoactivity first develops, and the extent to which each mural cell type contributes to vascular tone regulation during development. For the first time in an in vivo system, we highlight the dynamic changes in mural cell vasoactivity during development. We assess mural cell vasoactivity in the early zebrafish cerebral vasculature in response to pharmacological agents. We determine that pericyte-covered vessels constrict and dilate at 4 days post fertilization (dpf) but not at 6 dpf. The prostaglandin EP4 receptor contributes to pericyte-covered vessel dilation at 4 dpf. In contrast, vSMC-covered vessels constrict but do not dilate at 4 dpf. At 6 dpf, vSMC-covered vessels continue to constrict but only dilate from a pre-constricted state. Using genetic ablation, we demonstrate that mural cell contraction and relaxation is an active response by pericytes and vSMCs. Thus, we show that both pericytes and vSMCs have the ability to regulate cerebral vascular tone but at different stages of development. Pericytes are involved in regulating vessel diameters prior to the maturation of the vSMCs. Once vSMCs mature, pericytes are no longer active, and only vSMCs regulate vascular tone in the developing embryonic brain of zebrafish. The onset of vasoactivity of vSMCs corresponds to the development of increased neuronal activity and neurovascular coupling.

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Section: Discussionmentioning

confidence: 99%

Development of vascular myogenic responses in zebrafish

Bahrami

Childs

2019

Preprint

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“…Blocking cholinergic receptors with atropine caused ischemia in pancreatic capillary beds 21 . Under increased glucose levels, during which parasympathetic activity increases, more rapid islet blood flow occurs relative to decreased glucose levels 22,24 . Conversely, stimulation of adrenergic nerve fibers decreases pancreatic blood flow 5,24 .…”

Section: Discussionmentioning

confidence: 99%

“…Under increased glucose levels, during which parasympathetic activity increases, more rapid islet blood flow occurs relative to decreased glucose levels 22,24 . Conversely, stimulation of adrenergic nerve fibers decreases pancreatic blood flow 5,24 . The increase in blood flow under parasympathetic activity may contribute to increased insulin release, although precise links between islet blood flow and hormone secretion remain to be determined.…”

Section: Discussionmentioning

confidence: 99%

Optogenetic Stimulation of Pancreatic Function via Vagal Cholinergic Axons

Fontaine

Ramirez

Littich

et al. 2019

Preprint

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Previous studies have demonstrated stimulation of endocrine pancreas function by vagal nerve electrical stimulation. While this increases insulin secretion; concomitant reductions in circulating glucose do not occur. A complicating factor is the non-specific nature of electrical nerve stimulation. Optogenetic tools enable high specificity in neural stimulation using cell-type specific targeting of opsins and/or spatially shaped excitation light. Here, we demonstrate lightactivated stimulation of the endocrine pancreas by targeting vagal parasympathetic axons. In a mouse model expressing ChannelRhodopsin2 (ChR2) in cholinergic cells, serum insulin and glucose were measured in response to both ultrasound image-guided optical stimulation of axon terminals in the pancreas and optical stimulation of axons of the cervical vagus nerve, together with ultrasound-based measures of pancreas blood flow. Measurements were made in basalglucose and glucose-stimulated conditions. Significant increases in plasma insulin occurred relative to controls under both pancreas and vagal stimulation, accompanying rapid reductions in glycemic levels. Additionally, a significant increase in pancreatic blood flow was measured following optical stimulation. Together, these results demonstrate the utility of in-vivo optogenetics for studying the neural regulation of endocrine pancreas function and suggest therapeutic potential for the control of insulin secretion and glucose homeostasis.

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“…Although it appears that pericytes are required for normal insulin secretion, it is still unknown whether pericytes directly communicate with beta cells or whether the majority of these changes are mediated by pericytes manipulating capillary blood flow to beta cells. A recent publication by Almaca et al demonstrated that pericytes can regulate capillary diameter and blood flow to islets in response to factors such as endothelin‐1 . The same study went on to show that an increase in beta cell activity resulted in a decrease in pericyte activity, manifesting as capillary dilation .…”

Section: Pericytes and Capillary Blood Flowmentioning

confidence: 97%

Metabolic‐vascular coupling in skeletal muscle: A potential role for capillary pericytes?

Attrill

Ramsay

Ross

et al. 2019

Clin Exp Pharma Physio

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The matching of capillary blood flow to metabolic rate of the cells within organs and tissues is a critical microvascular function which ensures appropriate delivery of hormones and nutrients, and the removal of waste products. This relationship is particularly important in tissues where local metabolism, and hence capillary blood flow, must be regulated to avoid a mismatch between nutrient demand and supply that would compromise normal function. The consequences of a mismatch in microvascular blood flow and metabolism are acutely apparent in the brain and heart, where a sudden cessation of blood flow, for example following an embolism, acutely manifests as stroke or myocardial infarction. Even in more resilient tissues such as skeletal muscle, a short-term mismatch reduces muscle performance and exercise tolerance, and can cause intermittent claudication. In the longer-term, a microvascular-metabolic mismatch in skeletal muscle reduces insulin-mediated muscle glucose uptake, leading to disturbances in whole-body metabolic homeostasis. While the notion that capillary blood flow is fine-tuned to meet cellular metabolism is well accepted, the mechanisms that control this function and where and how different parts of the vascular tree contribute to capillary blood flow regulation remain poorly understood. Here, we discuss the emerging evidence implicating pericytes, mural cells that surround capillaries, as key mediators that match tissue metabolic demand with adequate capillary blood flow in a number of organs, including skeletal muscle. K E Y W O R D Scapillary blood flow, microvasculature, pericytes, skeletal muscle | 521 ATTRILL eT AL.

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The Pericyte of the Pancreatic Islet Regulates Capillary Diameter and Local Blood Flow

Cited by 152 publications

References 82 publications

Development of vascular myogenic responses in zebrafish

Development of vascular myogenic responses in zebrafish

Optogenetic Stimulation of Pancreatic Function via Vagal Cholinergic Axons

Metabolic‐vascular coupling in skeletal muscle: A potential role for capillary pericytes?

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