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

Jonathan R. Weitz, Madina Makhmutova, Joana Almaça, Julia Stertmann, Kristie Aamodt, Marcela Brissova, Stephan Speier, Rayner Rodriguez-Diaz, Alejandro Caicedo

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

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 Ca2+ 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.

Original languageEnglish (US)
Pages (from-to)182-192
Number of pages11
JournalDiabetologia
Volume61
Issue number1
DOIs
StatePublished - Jan 1 2018

Keywords

  • ATP
  • Beta cell
  • Calcium imaging
  • Macrophage
  • Pancreas
  • Purinergic
  • Tissue slice

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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