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.
Keywords:
beta-cell; islets.
© 2017 John Wiley & Sons Ltd.
Publication types
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Review
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Apoptosis
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Cell Communication*
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Cell Proliferation*
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Cellular Microenvironment*
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Diabetes Mellitus, Type 1 / metabolism
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Diabetes Mellitus, Type 1 / pathology
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Diabetes Mellitus, Type 2 / metabolism
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Diabetes Mellitus, Type 2 / pathology
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Extracellular Matrix / immunology
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Extracellular Matrix / metabolism
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Extracellular Matrix / pathology
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Glucagon-Secreting Cells / cytology
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Glucagon-Secreting Cells / immunology
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Glucagon-Secreting Cells / metabolism
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Glucagon-Secreting Cells / pathology
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Humans
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Insulin-Secreting Cells / cytology
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Insulin-Secreting Cells / immunology
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Insulin-Secreting Cells / metabolism*
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Insulin-Secreting Cells / pathology
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Islets of Langerhans / blood supply
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Islets of Langerhans / cytology*
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Islets of Langerhans / innervation
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Islets of Langerhans / pathology
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Macrophages / cytology
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Macrophages / immunology
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Macrophages / metabolism
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Macrophages / pathology
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Models, Biological*
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Pancreatic Polypeptide-Secreting Cells / cytology
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Pancreatic Polypeptide-Secreting Cells / immunology
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Pancreatic Polypeptide-Secreting Cells / metabolism
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Pancreatic Polypeptide-Secreting Cells / pathology
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Somatostatin-Secreting Cells / cytology
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Somatostatin-Secreting Cells / immunology
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Somatostatin-Secreting Cells / metabolism
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Somatostatin-Secreting Cells / pathology
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Species Specificity