The Role of Vascular Cells in Pancreatic Beta-Cell Function

Abstract

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.

Dysregulated insulin secretion is associated with pancreatic β‐cell hyperplasia and direct acinar‐β‐cell trans‐differentiation in partially eNOS ‐deficient mice

“…An abnormal endothelial function may cause a mismatch between insulin release and blood flow adjustment in islet microcirculation, resulting in dysregulated insulin secretion. Actually, a complex endothelial‐β‐cell functional axis has been postulated in pancreatic islets (Burganova et al, 2021 ; Hogan & Hull, 2017 ; Narayanan et al, 2017 ; Peiris et al, 2014 ). Islet endothelial cells produce factors (e.g., hepatocyte growth factor or connective tissue growth factor), that enhance β‐cell differentiation and proliferation (Oliveira et al, 2018 ; Riley et al, 2015 ) and others that influence insulin biosynthesis and/or release, such as NO, endothelin‐1 and extracellular matrix molecules (Gregersen et al, 1996 ; Hogan & Hull, 2017 ; Johansson et al, 2009 ; Nikolova et al, 2006 ).…”

Effects of Isorhamnetin on Diabetes and Its Associated Complications: A Review of In Vitro and In Vivo Studies and a Post Hoc Transcriptome Analysis of Involved Molecular Pathways

“…Insulin is a hormone naturally secreted by the body that helps our cells, particularly muscle cells, liver cells, adipose cells, and brain cells, absorb glucose from food to be converted into energy for all biological processes and functions [ 125 , 126 ]. In normal conditions, insulin is secreted by pancreatic β-cells, then released into the bloodstream.…”

Bioengineering the Vascularized Endocrine Pancreas: A Fine-Tuned Interplay Between Vascularization, Extracellular-Matrix-Based Scaffold Architecture, and Insulin-Producing Cells

“…ECs can directly affect β-cell function by upregulating insulin secretion and promoting β-cell survival via the secretion of soluble factors such as hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF)-A (36) and ECM proteins (37). Although the contribution of EC to islet endocrine function has been well described in the literature, the role of PC has recently been emphasized (35). Pericytes are abluminal mural cells embedded in the BM-ECM of blood vessels and play a key role in regulating endocrine niche homeostasis and function (35,37).…”

“…Although the contribution of EC to islet endocrine function has been well described in the literature, the role of PC has recently been emphasized (35). Pericytes are abluminal mural cells embedded in the BM-ECM of blood vessels and play a key role in regulating endocrine niche homeostasis and function (35,37). Indeed, Landsman et al, in a series of ablation experiments, reported the role of pericytes in β-cell expansion during the neonatal stage and in the maintenance of β-cell maturation and function in adulthood (38)(39)(40), regulating the production and deposition of islet ECM components and promoting the expression of β-cell genes including Ins1, Mafa, and Glut2 (41).…”

“…Vascular cells, such as endothelial cells (EC) and pericytes, generally constitute the cellular part of the tunica intima of vessels, while the structural part is the basement membrane (BM), which is constituted by a specific ECM. In the endocrine pancreatic niche, ECs form a fenestrated endothelium, guaranteeing high permeability (ten times more fenestrae compared to exocrine vessels) and a greater capacity for nutrients, hormones, oxygen, and metabolic waste exchange ( 34 , 35 ). ECs can directly affect β-cell function by upregulating insulin secretion and promoting β-cell survival via the secretion of soluble factors such as hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF)-A ( 36 ) and ECM proteins ( 37 ).…”