Human and mouse regenerative macrophages enhance beta cell survival, function, and proliferation.
Type 1 diabetes is caused by immune-mediated destruction of beta cells. Interestingly, individuals with long-standing type 1 diabetes have residual beta cells, suggesting regenerative mechanisms may help beta cell survival. Islet-resident macrophages have an important role in dia
- Authors
- Monajemi M, Craciun AS, Huang Q, Dai L, Mojibian M, Crome SQ, Verchere CB, Levings MK
- Journal
- Islets
- Published
- 2026-12-31
- DOI
- 10.1080/19382014.2026.2659457
- PMID
- 42070103
- Content type
- Paper
- Authority
- Academic
Abstract
Type 1 diabetes is caused by immune-mediated destruction of beta cells. Interestingly, individuals with long-standing type 1 diabetes have residual beta cells, suggesting regenerative mechanisms may help beta cell survival. Islet-resident macrophages have an important role in diabetes, and can adopt a tissue-regenerating phenotype that may support beta cells. However, the roles of macrophages in beta cell survival, function, and proliferation remain poorly defined. This study aimed to elucidate how macrophage subtypes influence beta cell survival, function, and proliferation. Mouse and human islets were isolated from the pancreas and co-cultured in vitro with macrophages. To investigate whether macrophages enhance beta cell survival and function, apoptosis was measured using flow cytometry, and insulin secretion was assessed via glucose-stimulated insulin secretion assays. We also examined whether macrophages increased beta cell proliferation in the presence of harmine, a DYRK1A inhibitor. Finally, we evaluated the effect of islet co-culture on macrophage phenotype by flow cytometry and cytokine secretion analysis. We found that regenerative, but not pro-inflammatory, macrophages enhanced beta cell survival and function through mechanisms that did not require direct cell contact. Direct contact between macrophages and islets promoted a macrophage regenerative phenotype characterized by increased CD206 expression and secretion of anti-inflammatory factors. Additionally, regenerative macrophages promoted beta cell proliferation in the presence of harmine. Our findings demonstrate that regenerative macrophages support pancreatic beta cell survival, function, and proliferation. Harnessing the regenerative properties of macrophages could offer a novel strategy to promote beta cell survival and function.
Citation
Monajemi M, Craciun AS, Huang Q, Dai L, Mojibian M, Crome SQ, Verchere CB, Levings MK (2026) Human and mouse regenerative macrophages enhance beta cell survival, function, and proliferation.. Islets. doi:10.1080/19382014.2026.2659457
DOI: 10.1080/19382014.2026.2659457
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