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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 Dalmas8
Estimated H-index: 8
+ 17 AuthorsMarc Y. Donath60
Estimated H-index: 60
Sources
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 (70)
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References58
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#1Catherine HajmrleH-Index: 8
#2Nancy SmithH-Index: 4
Last. Patrick E. MacDonaldH-Index: 36
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IL-1β is a well-established inducer of both insulin resistance and impaired pancreatic islet function. Despite this, findings examining IL-1 receptor deficiency or antagonism in in vivo animal models, as well as in clinical studies of type 2 diabetic (T2D) patients, have led to conflicting results, suggesting that the actions of IL-1β on glycemic control may be pleiotropic in nature. In the present work, we find that the ability of IL-1β to amplify glucose-stimulated insulin secretion from human...
17 CitationsSource
#1J. Breton (University of Rouen)H-Index: 11
#2Naouel Tennoune (University of Rouen)H-Index: 7
Last. Sergueï O. Fetissov (University of Rouen)H-Index: 32
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Summary The composition of gut microbiota has been associated with host metabolic phenotypes, but it is not known if gut bacteria may influence host appetite. Here we show that regular nutrient provision stabilizes exponential growth of E. coli , with the stationary phase occurring 20 min after nutrient supply accompanied by bacterial proteome changes, suggesting involvement of bacterial proteins in host satiety. Indeed, intestinal infusions of E. coli stationary phase proteins increased plasma ...
102 CitationsSource
BACKGROUND The effects of empagliflozin, an inhibitor of sodium–glucose cotransporter 2, in addition to standard care, on cardiovascular morbidity and mortality in patients with type 2 diabetes at high cardiovascular risk are not known. METHODS We randomly assigned patients to receive 10 mg or 25 mg of empagliflozin or placebo once daily. The primary composite outcome was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, as analyzed in the pooled empagliflozin...
2,995 CitationsSource
#1Dachuan Zhang (Yeshiva University)H-Index: 8
#2Grace Chen (Yeshiva University)H-Index: 2
Last. Paul S. Frenette (Yeshiva University)H-Index: 74
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Neutrophil ageing, which encourages inflammation and vaso-occlusion in a mouse model of sickle-cell disease, is shown to depend on the intestinal microbiota and activation of the TLR/Myd88 signalling pathways.
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#1Christopher Benner (Salk Institute for Biological Studies)H-Index: 44
#2Talitha van der Meulen (Salk Institute for Biological Studies)H-Index: 11
Last. Mark O. Huising (UC Davis: University of California, Davis)H-Index: 32
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Background Insulin producing beta cell and glucagon producing alpha cells are colocalized in pancreatic islets in an arrangement that facilitates the coordinated release of the two principal hormones that regulate glucose homeostasis and prevent both hypoglycemia and diabetes. However, this intricate organization has also complicated the determination of the cellular source(s) of the expression of genes that are detected in the islet. This reflects a significant gap in our understanding of mouse...
125 CitationsSource
#1Andrew N. Macintyre (Duke University)H-Index: 15
#2Valerie A. Gerriets (Duke University)H-Index: 15
Last. Jeffrey C. Rathmell (Duke University)H-Index: 59
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#1Yasutaka Okabe (Yale University)H-Index: 10
#2Ruslan Medzhitov (Yale University)H-Index: 102
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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
Last. Liza Makowski (UNC: University of North Carolina at Chapel Hill)H-Index: 30
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Glucose is a critical component in the proinflammatory response of macrophages (MΦs). However, the contribution of glucose transporters (GLUTs) and the mechanisms regulating subsequent glucose metabolism in the inflammatory response are not well understood. Because MΦs contribute to obesity-induced inflammation, it is important to understand how substrate metabolism may alter inflammatory function. We report that GLUT1 (SLC2A1) is the primary rate-limiting glucose transporter on proinflammatory-...
222 CitationsSource
#1Mohammed Herieka (University of Leicester)H-Index: 2
#2Clett Erridge (University of Leicester)H-Index: 19
Raised levels of circulating inflammatory markers are associated with coronary artery disease, obesity and type II diabetes. It has been proposed that the ingestion of high-fat meals may serve as a stimulus to raise systemic inflammatory tone, although interventional studies have yielded conflicting results. We here review 57 studies of high-fat meal induced acute postprandial inflammation to identify the most frequently reported markers of postprandial inflammation and to compare these results ...
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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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Low-grade inflammation in adipose tissue and liver has been implicated in obesity-associated insulin resistance and type 2 diabetes. Yet, the contribution of inflammatory cells to the pathogenesis of skeletal muscle insulin resistance remains elusive. In a large cohort of obese human individuals, blood monocyte Fas (CD95) expression correlated with systemic and skeletal muscle insulin resistance. To test a causal role for myeloid cell Fas expression in the development of skeletal muscle insulin ...
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Summary Postprandial hypoglycemia is a disabling complication of the treatment of obesity by gastric bypass surgery. So far, no therapy exists, and the underlying mechanisms remain unclear. Here, we hypothesized that glucose-induced IL-1β leads to an exaggerated insulin response in this condition. Therefore, we conducted a placebo-controlled, randomized, double-blind, crossover study with the SGLT2-inhibitor empagliflozin and the IL-1 receptor antagonist anakinra ( clinicaltrials.gov NCT03200782...
Source
#1Nadia Cobo-Vuilleumier (Pablo de Olavide University)H-Index: 10
#2Benoit R. Gauthier (Pablo de Olavide University)H-Index: 3
Abstract Type 1 diabetes mellitus (T1DM) is an autoimmune disease that targets the destruction of islet beta-cells resulting in insulin deficiency, hyperglycemia and death if untreated. Despite advances in medical devices and longer-acting insulin, there is still no robust therapy to substitute and protect beta-cells that are lost in T1DM. Attempts to refrain from the autoimmune attack have failed to achieve glycemic control in patients highlighting the necessity for a paradigm shift in T1DM tre...
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#1Friederike Schulze (University of Basel)H-Index: 4
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Gestational diabetes mellitus (GDM) is one of the most common diseases associated with pregnancy, however, the underlying mechanisms remain unclear. Based on the well documented role of inflammation in type 2 diabetes, the aim was to investigate the role of inflammation in GDM. We established a mouse model for GDM on the basis of its two major risk factors, obesity and aging. In these GDM mice, we observed increased Interleukin-1β (IL-1β) expression in the uterus and the placenta along with elev...
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#1Lucie Orliaguet (Paris V: Paris Descartes University)H-Index: 1
#2Elise Dalmas (Paris V: Paris Descartes University)
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Type-2 diabetes (T2D) is a disease of two aetiologies: metabolic and inflammatory. At the cross-section of these aetiologies lays the phenomenon of metabolic inflammation. Whilst metabolic inflammation is characterised as systemic, a common starting point is the tissue-resident macro-phage, who’s successful physiological or aberrant pathological adaptation to its microenvironment determines disease course and severity. This review will highlight the key mechanisms in macrophage polarisation, inf...
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#1Urszula Brykczynska (ETH Zurich)
#2Marco Geigges (ETH Zurich)H-Index: 1
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#1Wei Ying (UCSD: University of California, San Diego)H-Index: 12
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Inflammasomes are intracellular multiprotein complexes in the cytoplasm that regulate inflammation activation in the innate immune system in response to pathogens and to host self-derived molecules. Recent advances greatly improved our understanding of the activation of nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasomes at the molecular level. The NLRP3 belongs to the subfamily of NLRP which activates caspase 1, thus causing the p...
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