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Weitz, J.R.* ; Makhmutova, M.* ; Almaça, J.* ; Stertmann, J. ; Aamodt, K.* ; Brissova, M.* ; Speier, S. ; Rodriguez-Diaz, R.* ; Caicedo, A.*

Mouse pancreatic islet macrophages use locally released ATP to monitor beta cell activity.

Diabetologia 61, 1-11 (2018)
Publ. Version/Full Text Research data DOI
Aims/hypothesis: Tissue-resident macrophages sense the microenvironment and respond by producing signals that act locally to maintain a stable tissue state. It is now known that pancreatic islets contain their own unique resident macrophages, which have been shown to promote proliferation of the insulin-secreting beta cell. However, it is unclear how beta cells communicate with islet-resident macrophages. Here we hypothesised that islet macrophages sense changes in islet activity by detecting signals derived from beta cells. Methods: To investigate how islet-resident macrophages respond to cues from the microenvironment, we generated mice expressing a genetically encoded Ca 2+ indicator in myeloid cells. We produced living pancreatic slices from these mice and used them to monitor macrophage responses to stimulation of acinar, neural and endocrine cells. Results: Islet-resident macrophages expressed functional purinergic receptors, making them exquisite sensors of interstitial ATP levels. Indeed, islet-resident macrophages responded selectively to ATP released locally from beta cells that were physiologically activated with high levels of glucose. Because ATP is co-released with insulin and is exclusively secreted by beta cells, the activation of purinergic receptors on resident macrophages facilitates their awareness of beta cell secretory activity. Conclusions/interpretation: Our results indicate that islet macrophages detect ATP as a proxy signal for the activation state of beta cells. Sensing beta cell activity may allow macrophages to adjust the secretion of factors to promote a stable islet composition and size.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Atp ; Beta Cell ; Calcium Imaging ; Macrophage ; Pancreas ; Purinergic ; Tissue Slice; Insulin-secretion; In-vivo; Dendritic Cells; Tissue-slices; Brain-injury; Alpha Cells; Inflammation; Mice; Langerhans; Receptors
ISSN (print) / ISBN 0012-186X
e-ISSN 1432-0428
Journal Diabetologia
Quellenangaben Volume: 61, Issue: 1, Pages: 1-11 Article Number: , Supplement: ,
Publisher Springer
Publishing Place Berlin ; Heidelberg [u.a.]
Reviewing status Peer reviewed
Institute(s) Institute for Pancreatic Beta Cell Research (IPI)