Molecular and functional profiling of human islets: from heterogeneity to human phenotypes
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REVIEW
Molecular and functional profiling of human islets: from heterogeneity to human phenotypes Rafael Arrojo e Drigo 1
&
Birbickram Roy 2,3
&
Patrick E. MacDonald 2,3
Received: 2 March 2020 / Accepted: 6 April 2020 / Published online: 31 August 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Efforts to phenotype pancreatic islets have contributed tremendously to our present understanding of endocrine function and diabetes. A continued evolution in approaches to study islet physiology is important given the need to establish reference points for mature islet functionality, understanding biological variation amongst individuals and cells, and the ongoing appreciation of the role for islets in diabetes susceptibility. Recent efforts in islet biology have focused on technological improvements in imaging, molecular profiling and data analysis, along with a push for enhanced transparency and reporting. The integration of these approaches within a classical islet physiology framework, and approaches to link these data with in vivo human phenotypes, will be critical as we move towards a better understanding of islet function in health and disease. Here we discuss what we feel are important issues and useful approaches to consider as we move forward as a field in islet and beta cell phenotyping.
Keywords Diabetes . Glucagon . Human . Insulin . Islets of Langerhans . Phenotyping, cellular heterogeneity . Review . Single cell Abbreviations ADI Alberta Diabetes Institute GWAS Genome-wide association study HPAP Human Pancreas Analysis Program IIDP Integrated Islet Distribution Program scRNA-seq Single-cell RNA sequencing
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00125-020-05159-8) contains a slide of the figure for download, which is available to authorised users. * Patrick E. MacDonald [email protected] 1
Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA
2
Department of Pharmacology, University of Alberta, Edmonton, AB, Canada
3
Alberta Diabetes Institute, LKS Centre, University of Alberta, Rm. 6-112, Edmonton, AB T6G 2E1, Canada
Introduction Through a series of electrical, Ca2+ and molecular signalling processes, endocrine cells within the pancreatic islets of Langerhans regulate the release of key metabolismregulating hormones. Early characterisation of these cells primarily consisted of histopathological analyses and indirect assessment of beta cell activity by measurement of circulating hormones or C-peptide. Modelling extended these measurements to extract indices of islet function [1]. Dynamic measurements in vivo and in isolated perfused pancreases provided key insights into islet function, such as the dynamic properties of insulin release and its Ca2+-dependence, yielding models of biphasic insulin secretion that remain foundational [2]. The establishment of methods to isolate islets, first by microdissection and then by digestion and density centrifugation, ushered in a new
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