title: Concise Review: Macrophages: Versatile Gatekeepers During Pancreatic β-Cell Development, Injury, and Regeneration.
abstract: Macrophages are classically considered detrimental for pancreatic β-cell survival and function, thereby contributing to β-cell failure in both type 1 (T1D) and 2 (T2D) diabetes mellitus. In addition, adipose tissue macrophages negatively influence peripheral insulin signaling and promote obesity-induced insulin resistance in T2D. In contrast, recent data unexpectedly uncovered that macrophages are not only able to protect β cells during pancreatitis but also to orchestrate β-cell proliferation and regeneration after β-cell injury. Moreover, by altering their activation state, macrophages are able to improve insulin resistance in murine models of T2D. This review will elaborate on current insights in macrophage heterogeneity and on the evolving role of pancreas macrophages during organogenesis, tissue injury, and repair. Additional identification of macrophage subtypes and of their secreted factors might ultimately translate into novel therapeutic strategies for both T1D and T2D.
  
  
  CONCLUSIONS
  Diabetes mellitus is a pandemic disease, characterized by severe acute and chronic complications. Macrophages have long been considered prime suspects in the pathogenesis of both type 1 and 2 diabetes mellitus. In this concise review, current insights in macrophage heterogeneity and on the, as yet, underappreciated role of alternatively activated macrophages in insulin sensing and β-cell development/repair are reported. Further identification of macrophage subtypes and of their secreted factors might ultimately translate into novel therapeutic strategies for diabetes mellitus.
authors.affiliation: Diabetes Research Center and Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium; Division of Pediatric Endocrinology, Department of Pediatrics, Ghent University Hospital, and Department of Pediatrics and Genetics, Ghent University, Ghent, Belgium; Myeloid Cell Immunology Laboratory, VIB, Brussels, Belgium; Department of Endocrinology, Universitair Ziekenhuis Brussel, Brussels, Belgium.
authors.forename: Naomi
authors.initials: N
authors.lastname: Van Gassen
authors.affiliation: Diabetes Research Center and Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium; Division of Pediatric Endocrinology, Department of Pediatrics, Ghent University Hospital, and Department of Pediatrics and Genetics, Ghent University, Ghent, Belgium; Myeloid Cell Immunology Laboratory, VIB, Brussels, Belgium; Department of Endocrinology, Universitair Ziekenhuis Brussel, Brussels, Belgium.
authors.forename: Willem
authors.initials: W
authors.lastname: Staels
authors.affiliation: Diabetes Research Center and Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium; Division of Pediatric Endocrinology, Department of Pediatrics, Ghent University Hospital, and Department of Pediatrics and Genetics, Ghent University, Ghent, Belgium; Myeloid Cell Immunology Laboratory, VIB, Brussels, Belgium; Department of Endocrinology, Universitair Ziekenhuis Brussel, Brussels, Belgium.
authors.forename: Eva
authors.initials: E
authors.lastname: Van Overmeire
authors.affiliation: Diabetes Research Center and Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium; Division of Pediatric Endocrinology, Department of Pediatrics, Ghent University Hospital, and Department of Pediatrics and Genetics, Ghent University, Ghent, Belgium; Myeloid Cell Immunology Laboratory, VIB, Brussels, Belgium; Department of Endocrinology, Universitair Ziekenhuis Brussel, Brussels, Belgium.
authors.forename: Sofie
authors.initials: S
authors.lastname: De Groef
authors.affiliation: Diabetes Research Center and Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium; Division of Pediatric Endocrinology, Department of Pediatrics, Ghent University Hospital, and Department of Pediatrics and Genetics, Ghent University, Ghent, Belgium; Myeloid Cell Immunology Laboratory, VIB, Brussels, Belgium; Department of Endocrinology, Universitair Ziekenhuis Brussel, Brussels, Belgium.
authors.forename: Mozhdeh
authors.initials: M
authors.lastname: Sojoodi
authors.affiliation: Diabetes Research Center and Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium; Division of Pediatric Endocrinology, Department of Pediatrics, Ghent University Hospital, and Department of Pediatrics and Genetics, Ghent University, Ghent, Belgium; Myeloid Cell Immunology Laboratory, VIB, Brussels, Belgium; Department of Endocrinology, Universitair Ziekenhuis Brussel, Brussels, Belgium.
authors.forename: Yves
authors.initials: Y
authors.lastname: Heremans
authors.affiliation: Diabetes Research Center and Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium; Division of Pediatric Endocrinology, Department of Pediatrics, Ghent University Hospital, and Department of Pediatrics and Genetics, Ghent University, Ghent, Belgium; Myeloid Cell Immunology Laboratory, VIB, Brussels, Belgium; Department of Endocrinology, Universitair Ziekenhuis Brussel, Brussels, Belgium.
authors.forename: Gunter
authors.initials: G
authors.lastname: Leuckx
authors.affiliation: Diabetes Research Center and Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium; Division of Pediatric Endocrinology, Department of Pediatrics, Ghent University Hospital, and Department of Pediatrics and Genetics, Ghent University, Ghent, Belgium; Myeloid Cell Immunology Laboratory, VIB, Brussels, Belgium; Department of Endocrinology, Universitair Ziekenhuis Brussel, Brussels, Belgium.
authors.forename: Mark
authors.initials: M
authors.lastname: Van de Casteele
authors.affiliation: Diabetes Research Center and Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium; Division of Pediatric Endocrinology, Department of Pediatrics, Ghent University Hospital, and Department of Pediatrics and Genetics, Ghent University, Ghent, Belgium; Myeloid Cell Immunology Laboratory, VIB, Brussels, Belgium; Department of Endocrinology, Universitair Ziekenhuis Brussel, Brussels, Belgium.
authors.forename: Jo A
authors.initials: JA
authors.lastname: Van Ginderachter
authors.affiliation: Diabetes Research Center and Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium; Division of Pediatric Endocrinology, Department of Pediatrics, Ghent University Hospital, and Department of Pediatrics and Genetics, Ghent University, Ghent, Belgium; Myeloid Cell Immunology Laboratory, VIB, Brussels, Belgium; Department of Endocrinology, Universitair Ziekenhuis Brussel, Brussels, Belgium Harry.Heimberg@vub.ac.be Nico.De.Leu@vub.ac.be.
authors.forename: Harry
authors.initials: H
authors.lastname: Heimberg
authors.affiliation: Diabetes Research Center and Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium; Division of Pediatric Endocrinology, Department of Pediatrics, Ghent University Hospital, and Department of Pediatrics and Genetics, Ghent University, Ghent, Belgium; Myeloid Cell Immunology Laboratory, VIB, Brussels, Belgium; Department of Endocrinology, Universitair Ziekenhuis Brussel, Brussels, Belgium Harry.Heimberg@vub.ac.be Nico.De.Leu@vub.ac.be.
authors.forename: Nico
authors.initials: N
authors.lastname: De Leu
mesh_terms: D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D010195:Pancreatitis / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D012038:Regeneration
keywords: Development; Injury; Macrophage; Pancreas; Regeneration; β Cell
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