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Postprandial macrophage-derived IL-1β stimulates insulin, and both synergistically promote glucose disposal and inflammation

Published on Mar 1, 2017in Nature Immunology23.53
· DOI :10.1038/ni.3659
Erez Dror7
Estimated H-index: 7
,
Elise Dalmas7
Estimated H-index: 7
+ 17 AuthorsMarc Y. Donath57
Estimated H-index: 57
Abstract
The deleterious effect of chronic activation of the IL-1β system on type 2 diabetes and other metabolic diseases is well documented. However, a possible physiological role for IL-1β in glucose metabolism has remained unexplored. Here we found that feeding induced a physiological increase in the number of peritoneal macrophages that secreted IL-1β, in a glucose-dependent manner. Subsequently, IL-1β contributed to the postprandial stimulation of insulin secretion. Accordingly, lack of endogenous IL-1β signaling in mice during refeeding and obesity diminished the concentration of insulin in plasma. IL-1β and insulin increased the uptake of glucose into macrophages, and insulin reinforced a pro-inflammatory pattern via the insulin receptor, glucose metabolism, production of reactive oxygen species, and secretion of IL-1β mediated by the NLRP3 inflammasome. Postprandial inflammation might be limited by normalization of glycemia, since it was prevented by inhibition of the sodium-glucose cotransporter SGLT2. Our findings identify a physiological role for IL-1β and insulin in the regulation of both metabolism and immunity.
  • References (58)
  • Citations (56)
References58
Newest
#1Dachuan Zhang (Yeshiva University)H-Index: 8
#2Grace Chen (Yeshiva University)H-Index: 2
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#1Alex J. Freemerman (UNC: University of North Carolina at Chapel Hill)H-Index: 9
#2Amy R. Johnson (UNC: University of North Carolina at Chapel Hill)H-Index: 13
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#1Christopher Benner (Salk Institute for Biological Studies)H-Index: 41
#2Talitha van der Meulen (Salk Institute for Biological Studies)H-Index: 11
Last.Mark O. Huising (Salk Institute for Biological Studies)H-Index: 31
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#1Stephan Wueest (Boston Children's Hospital)H-Index: 15
#2Rouven Mueller (UZH: University of Zurich)H-Index: 1
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#1Pu Hong (Southern Medical University)
#2Ruo-Nan Gu (Southern Medical University)H-Index: 1
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#2Charles A. Dinarello (CU: University of Colorado Boulder)H-Index: 173
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#1Gernot Schabbauer (Medical University of Vienna)H-Index: 25
#2Omar Sharif (Medical University of Vienna)H-Index: 15
Last.Andrea Vogel (Medical University of Vienna)H-Index: 1
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#1Marc Y. Donath (University of Basel)H-Index: 57
#2Daniel T. Meier (University of Basel)H-Index: 2
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#1Paola de CandiaH-Index: 9
Last.Teresa Micillo (University of Naples Federico II)H-Index: 2
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