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 language | English (US) |
|---|---|
| Pages (from-to) | 1-11 |
| Number of pages | 11 |
| Journal | Diabetologia |
| DOIs | |
| State | Accepted/In press - Sep 7 2017 |
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Keywords
- ATP
- Beta cell
- Calcium imaging
- Macrophage
- Pancreas
- Purinergic
- Tissue slice
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
Cite this
Mouse pancreatic islet macrophages use locally released ATP to monitor beta cell activity. / Weitz, Jonathan R.; Makhmutova, Madina; Almaca, Joana; Stertmann, Julia; Aamodt, Kristie; Brissova, Marcela; Speier, Stephan; Rodriguez Diaz, Rayner; Caicedo-Vierkant, Diego A.
In: Diabetologia, 07.09.2017, p. 1-11.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mouse pancreatic islet macrophages use locally released ATP to monitor beta cell activity
AU - Weitz, Jonathan R.
AU - Makhmutova, Madina
AU - Almaca, Joana
AU - Stertmann, Julia
AU - Aamodt, Kristie
AU - Brissova, Marcela
AU - Speier, Stephan
AU - Rodriguez Diaz, Rayner
AU - Caicedo-Vierkant, Diego A
PY - 2017/9/7
Y1 - 2017/9/7
N2 - 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.
AB - 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.
KW - ATP
KW - Beta cell
KW - Calcium imaging
KW - Macrophage
KW - Pancreas
KW - Purinergic
KW - Tissue slice
UR - http://www.scopus.com/inward/record.url?scp=85028991651&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85028991651&partnerID=8YFLogxK
U2 - 10.1007/s00125-017-4416-y
DO - 10.1007/s00125-017-4416-y
M3 - Article
C2 - 28884198
AN - SCOPUS:85028991651
SP - 1
EP - 11
JO - Diabetologia
JF - Diabetologia
SN - 0012-186X
ER -