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.
Significance: 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.
Keywords: Diabetes; Macrophage polarization; Macrophages; β-Cell proliferation; β-Cell regeneration.
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