Islet macrophages are the primary islet source of IGF-1 and improve glucose homeostasis following pancreatic beta-cell death.

Nackiewicz, D.; Dan, M.; Speck, M.; Chow, S.; Pospisilik, J. A.; Verchere, B.; Ehses, J.

doi:10.1101/480368

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bioRxiv · 10.1101/480368

Islet macrophages are the primary islet source of IGF-1 and improve glucose homeostasis following pancreatic beta-cell death.

Nackiewicz, D.·Dan, M.·Speck, M.·Chow, S.·Pospisilik, J. A.·Verchere, B.·Ehses, J.

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Abstract

Macrophages play a dynamic role in tissue repair following injury. Here we found that following streptozotocin (STZ)-induced beta-cell death, mouse islet macrophages expressed increased Igf1, decreased proinflammatory cytokine expression, and transcriptome changes consistent with macrophages undergoing efferocytosis and having an enhanced state of metabolism. Macrophages were the major, if not sole, contributors to islet IGF-1 production. Adoptive transfer experiments showed that macrophages can maintain insulin secretion in vivo following beta-cell death with no effects on islet-cell turnover. IGF-1 neutralization during STZ-treatment decreased insulin secretion without affecting islet-cell apoptosis or proliferation. Interestingly, high fat diet (HFD) combined with STZ further skewed islet macrophages to a reparative state. Finally, islet macrophages from db/db mice also expressed decreased proinflammatory cytokines and increased Igf1 mRNA. These data have important implications for islet biology and pathology and show that islet macrophages preserve their reparative state following beta-cell death even during HFD feeding and severe hyperglycemia.

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Nackiewicz, D., Dan, M., Speck, M., Chow, S., Pospisilik, J. A., Verchere, B., Ehses, J.. 2018-11-27. Islet macrophages are the primary islet source of IGF-1 and improve glucose homeostasis following pancreatic beta-cell death.. https://doi.org/10.1101/480368

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