title: Concise Review: New Insights Into the Role of Macrophages in β-Cell Proliferation.
abstract: Diabetes mellitus can potentially be treated with islet transplantation, but additional sources of β cells are necessary to overcome the short supply of donor pancreases. Although controversy still exists, it is generally believed that the postnatal expansion of the β-cell mass is mainly through pre-existing β-cell replication. Thus, understanding the molecular mechanisms underlying the regulation of β-cell proliferation might lead to clinical strategies for increasing β-cell numbers, both in vitro and in vivo. Macrophages have a well-recognized role in the development of insulitis as part of the pathogenesis of type 1 diabetes. However, a potential role for macrophage polarization, triggered by specific environmental stimuli, in promoting β-cell proliferation has only recently been appreciated. In the present review, we discuss several independent studies, using different regeneration models, that demonstrate a substantial inductive role for macrophages in β-cell proliferation. Additional dissection of the involved cell-cell crosstalk through specific signal transduction pathways is expected to improve our understanding of β-cell proliferation and might facilitate the current β-cell replacement therapy.
  
  
  CONCLUSIONS
  New independent findings from different β-cell regeneration models, contributed by different research groups, have provided compelling evidence to highlight a previously unappreciated role for macrophages in β-cell proliferation. Additional dissection of the underlying mechanisms and cell-cell crosstalk might shed new light on strategies to increase the functional β-cell mass in vivo and on β-cell replacement therapies.
authors.affiliation: Division of Pediatric Surgery, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA Xiangwei.xiao@chp.edu gittesgk@upmc.edu.
authors.forename: Xiangwei
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Division of Pediatric Surgery, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA Xiangwei.xiao@chp.edu gittesgk@upmc.edu.
authors.forename: George K
authors.initials: GK
authors.lastname: Gittes
mesh_terms: D000818:Animals; D002450:Cell Communication; D049109:Cell Proliferation; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction
keywords: Diabetes; Macrophage polarization; Macrophages; β-Cell proliferation; β-Cell regeneration