Beta cell dysfunction in diabetes: the islet microenvironment as an unusual suspect
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REVIEW
Beta cell dysfunction in diabetes: the islet microenvironment as an unusual suspect Joana Almaça 1
&
Alejandro Caicedo 1
&
Limor Landsman 2
Received: 6 February 2020 / Accepted: 22 April 2020 / Published online: 31 August 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Cells in different tissues, including endocrine cells in the pancreas, live in complex microenvironments that are rich in cellular and acellular components. Intricate interactions with their microenvironment dictate most cellular properties, such as their function, structure and size, and maintain tissue homeostasis. Pancreatic islets are populated by endocrine, vascular and immune cells that are immersed in the extracellular matrix. While the intrinsic properties of beta cells have been vastly investigated, our understanding of their interactions with their surroundings has only recently begun to unveil. Here, we review current research on the interplay between the islet cellular and acellular components, and the role these components play in beta cell physiology and pathophysiology. Although beta cell failure is a key pathomechanism in diabetes, its causes are far from being fully elucidated. We, thus, propose deleterious alterations of the islet niche as potential underlying mechanisms contributing to beta cell failure. In sum, this review emphasises that the function of the pancreatic islet depends on all of its components.
Keywords Extracellular matrix . Homeostasis . Microenvironment . Pancreatic islet . Pericytes . Review Abbreviations ECM Extracellular matrix IAPP Islet amyloid polypeptide mTOR Mammalian target of rapamycin NGF Nerve growth factor TCF7L2 Transcription factor 7-like 2 VEGF-A Vascular endothelial growth factor-A
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00125-020-05186-5) contains a slideset of the figures for download, which is available to authorised users. * Joana Almaça [email protected] * Alejandro Caicedo [email protected] * Limor Landsman [email protected] 1
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Miami Miller School of Medicine, 1580 NW 10th avenue, Miami, FL 33136, USA
2
Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel
Introduction The main cellular compartment in charge of the specific tissue function of an organ is the parenchyma, which in the pancreatic islet consists of the endocrine cell mass. Endocrine cells of the pancreas, however, do not exist in a vacuum. The endocrine parenchyma is infiltrated by vascular cells that form capillary tubes, thus connecting the organ to the systemic circulation. The parenchymal and vascular elements are immersed in a web of macromolecules, the extracellular matrix (ECM). Within this matrix, stretched between blood vessels and the parenchyma, live other cells, such as fibroblasts and macrophages. The microenvironment is not only a scaffold
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