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      Signals in the pancreatic islet microenvironment influence β-cell proliferation : AAMODTet al.

      1 , 1 , 2 , 3
      Diabetes, Obesity and Metabolism
      Wiley

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          Abstract

          The progressive loss of pancreatic β-cell mass that occurs in both type 1 and type 2 diabetes is a primary factor driving efforts to identify strategies for effectively increasing, enhancing or restoring β-cell mass. While factors that seem to influence β-cell proliferation in specific contexts have been described, reliable stimulation of human β-cell proliferation has remained a challenge. Importantly, β-cells exist in the context of a complex, integrated pancreatic islet microenvironment where they interact with other endocrine cells, vascular endothelial cells, extracellular matrix, neuronal projections and islet macrophages. This review highlights different components of the pancreatic microenvironment, and reviews what is known about how signaling that occurs between β-cells and these other components influences β-cell proliferation. Future efforts to further define the role of the pancreatic islet microenvironment on β-cell proliferation may lead to the development of successful approaches to increase or restore β-cell mass in diabetes.

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          Most cited references118

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          The emergence of tissue engineering raises new possibilities for the study of complex physiological and pathophysiological processes in vitro. Many tools are now available to create 3D tissue models in vitro, but the blueprints for what to make have been slower to arrive. We discuss here some of the 'design principles' for recreating the interwoven set of biochemical and mechanical cues in the cellular microenvironment, and the methods for implementing them. We emphasize applications that involve epithelial tissues for which 3D models could explain mechanisms of disease or aid in drug development.
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              Beta-cell replication is the primary mechanism subserving the postnatal expansion of beta-cell mass in humans.

              Little is known about the capacity, mechanisms, or timing of growth in beta-cell mass in humans. We sought to establish if the predominant expansion of beta-cell mass in humans occurs in early childhood and if, as in rodents, this coincides with relatively abundant beta-cell replication. We also sought to establish if there is a secondary growth in beta-cell mass coincident with the accelerated somatic growth in adolescence. To address these questions, pancreas volume was determined from abdominal computer tomographies in 135 children aged 4 weeks to 20 years, and morphometric analyses were performed in human pancreatic tissue obtained at autopsy from 46 children aged 2 weeks to 21 years. We report that 1) beta-cell mass expands by severalfold from birth to adulthood, 2) islets grow in size rather than in number during this transition, 3) the relative rate of beta-cell growth is highest in infancy and gradually declines thereafter to adulthood with no secondary accelerated growth phase during adolescence, 4) beta-cell mass (and presumably growth) is highly variable between individuals, and 5) a high rate of beta-cell replication is coincident with the major postnatal expansion of beta-cell mass. These data imply that regulation of beta-cell replication during infancy plays a major role in beta-cell mass in adult humans.
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                Author and article information

                Journal
                Diabetes, Obesity and Metabolism
                Diabetes Obes Metab
                Wiley
                14628902
                September 2017
                September 2017
                September 07 2017
                : 19
                : 124-136
                Affiliations
                [1 ]Department of Molecular Physiology and Biophysics; Vanderbilt University School of Medicine; Nashville TN
                [2 ]Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine; Vanderbilt University Medical Center; Nashville TN
                [3 ]VA Tennessee Valley Healthcare System; Nashville TN
                Article
                10.1111/dom.13031
                5679109
                28880471
                c34d5d4e-4c0f-40aa-9906-4538d1739072
                © 2017

                http://doi.wiley.com/10.1002/tdm_license_1.1

                http://onlinelibrary.wiley.com/termsAndConditions#vor

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