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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 Immunology 23.53
· 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
Cite
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)
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References58
Newest
Published on Apr 7, 2016in JCI insight
Catherine Hajmrle8
Estimated H-index: 8
,
Nancy Smith5
Estimated H-index: 5
+ 5 AuthorsPatrick E. MacDonald26
Estimated H-index: 26
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...
Published on Feb 1, 2016in Cell Metabolism 22.41
J. Breton11
Estimated H-index: 11
(University of Rouen),
Naouel Tennoune7
Estimated H-index: 7
(University of Rouen)
+ 17 AuthorsMartine Pestel-Caron17
Estimated H-index: 17
(University of Rouen)
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 ...
Published on Nov 26, 2015in The New England Journal of Medicine 70.67
Bernard Zinman7
Estimated H-index: 7
,
Christoph Wanner76
Estimated H-index: 76
+ 9 AuthorsHans-Juergen Woerle58
Estimated H-index: 58
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...
Published on Sep 1, 2015in Nature 43.07
Dachuan Zhang8
Estimated H-index: 8
(Yeshiva University),
Grace Chen2
Estimated H-index: 2
(Yeshiva University)
+ 9 AuthorsChristoph Scheiermann22
Estimated H-index: 22
(LMU: Ludwig Maximilian University of Munich)
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.
Published on Jul 1, 2014in Cell Metabolism 22.41
Andrew N. Macintyre15
Estimated H-index: 15
(Duke University),
Valerie A. Gerriets15
Estimated H-index: 15
(Duke University)
+ 8 AuthorsLaura P. Hale47
Estimated H-index: 47
(Duke University)
Summary CD4 T cell activation leads to proliferation and differentiation into effector (Teff) or regulatory (Treg) cells that mediate or control immunity. While each subset prefers distinct glycolytic or oxidative metabolic programs in vitro, requirements and mechanisms that control T cell glucose uptake and metabolism in vivo are uncertain. Despite expression of multiple glucose transporters, Glut1 deficiency selectively impaired metabolism and function of thymocytes and Teff. Resting T cells w...
Published on May 1, 2014in Cell 36.22
Yasutaka Okabe10
Estimated H-index: 10
(Yale University),
Ruslan Medzhitov100
Estimated H-index: 100
(Yale University)
Summary Tissue-resident macrophages are highly heterogeneous in terms of their functions and phenotypes as a consequence of adaptation to different tissue environments. Local tissue-derived signals are thought to control functional polarization of resident macrophages; however, the identity of these signals remains largely unknown. It is also unknown whether functional heterogeneity is a result of irreversible lineage-specific differentiation or a consequence of continuous but reversible inducti...
Published on Mar 14, 2014in Journal of Biological Chemistry
Alex J. Freemerman9
Estimated H-index: 9
(UNC: University of North Carolina at Chapel Hill),
Amy R. Johnson13
Estimated H-index: 13
(UNC: University of North Carolina at Chapel Hill)
+ 7 AuthorsLiza Makowski29
Estimated H-index: 29
(UNC: University of North Carolina at Chapel Hill)
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-...
Published on Jan 1, 2014in Molecular Nutrition & Food Research 4.65
Mohammed Herieka2
Estimated H-index: 2
(University of Leicester),
Clett Erridge20
Estimated H-index: 20
(University of Leicester)
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 ...
Published on Jan 1, 2014in BMC Genomics 3.50
Christopher Benner41
Estimated H-index: 41
(Salk Institute for Biological Studies),
Talitha van der Meulen11
Estimated H-index: 11
(Salk Institute for Biological Studies)
+ 3 AuthorsMark O. Huising31
Estimated H-index: 31
(Salk Institute for Biological Studies)
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...
Published on Jan 1, 2014in Embo Molecular Medicine 10.62
Stephan Wueest15
Estimated H-index: 15
(Boston Children's Hospital),
Rouven Mueller1
Estimated H-index: 1
(UZH: University of Zurich)
+ 9 AuthorsEugen J. Schoenle40
Estimated H-index: 40
(Boston Children's Hospital)
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 ...
Cited By56
Newest
Published in Molecular and Cellular Endocrinology 3.69
Adriana Ibarra Urizar2
Estimated H-index: 2
(UCPH: University of Copenhagen),
Michala Prause5
Estimated H-index: 5
(UCPH: University of Copenhagen)
+ -3 AuthorsNils Billestrup34
Estimated H-index: 34
(UCPH: University of Copenhagen)
Abstract Decreased insulin secretory capacity in Type 2 diabetes mellitus is associated with beta-cell dedifferentiation and inflammation. We hypothesize that prolonged exposure of beta-cells to low concentrations of IL-1β induce beta-cell dedifferentiation characterized by impaired glucose-stimulated insulin secretion, reduced expression of key beta-cell genes and changes in histone modifications at gene loci known to affect beta-cell function. Ten days exposure to IL-1β at non-cytotoxic concen...
Published in Frontiers in Immunology 4.72
Gernot Schabbauer25
Estimated H-index: 25
(Medical University of Vienna),
Omar Sharif15
Estimated H-index: 15
(Medical University of Vienna)
+ -3 AuthorsAndrea Vogel1
Estimated H-index: 1
(Medical University of Vienna)
Class 1 Phosphoinositide-3-Kinases (PI3Ks) have been widely studied and mediate essential roles in cellular proliferation, chemotaxis, insulin sensitivity and immunity. Here, we provide a comprehensive overview of how macrophage expressed PI3Ks and their downstream pathways orchestrate responses to metabolic stimuli and nutrients, polarizing macrophages, shaping their cellular identity and function. Particular emphasis will be given to adipose tissue macrophages, crucial players of insulin resis...
Published on Apr 25, 2019in Endocrine Reviews 15.17
Marc Y. Donath57
Estimated H-index: 57
(University of Basel),
Daniel T. Meier2
Estimated H-index: 2
(University of Basel),
Marianne Böni-Schnetzler21
Estimated H-index: 21
(University of Basel)
Published on Jan 1, 2019in Frontiers in Endocrinology 3.63
Paola de Candia9
Estimated H-index: 9
,
Francesco Prattichizzo14
Estimated H-index: 14
+ 11 AuthorsTeresa Micillo2
Estimated H-index: 2
(University of Naples Federico II)
Type 2 diabetes (T2D) is characterized by a progressive status of chronic, low-grade inflammation that accompanies the whole trajectory of the disease, from its inception to complication development. Accumulating evidence is disclosing a long list of possible "triggers" of inflammatory responses, many of which are promoted by unhealthy lifestyle choices and advanced age. Diabetic patients show an altered number and function of immune cells, of both innate and acquired immunity. Reactive autoanti...
Published on May 28, 2019in Seminars in Immunopathology 6.80
Milica Popovic1
Estimated H-index: 1
,
Gideon Sartorius , Mirjam Christ-Crain52
Estimated H-index: 52
The polycystic ovary syndrome (PCOS) is a frequent endocrine disorder in women of reproductive age. Its main characteristics are the ovarian overproduction of androgens and ovulatory dysfunction which lead to severe symptoms such as hirsutism, acne, insulin resistance, and infertility. Despite the frequency and disease burden of PCOS, its underlying causes remain unknown, and no causal therapeutic options are available. In recent years, several studies have shown that women with PCOS present wit...
Published on Jun 14, 2019in Cell Research 17.85
Qin Zhang2
Estimated H-index: 2
(CAS: Chinese Academy of Sciences),
Ying Pan2
Estimated H-index: 2
(CAS: Chinese Academy of Sciences)
+ 11 AuthorsZhuo-Xian Meng (ZJU: Zhejiang University)
Long-range communication between intestinal symbiotic bacteria and extra-intestinal organs can occur through circulating bacterial signal molecules, through neural circuits, or through cytokines or hormones from host cells. Here we report that Nod1 ligands derived from intestinal bacteria act as signal molecules and directly modulate insulin trafficking in pancreatic beta cells. The cytosolic peptidoglycan receptor Nod1 and its downstream adapter Rip2 are required for insulin trafficking in beta...
Published on Apr 5, 2019in Seminars in Immunopathology 6.80
Elise Dalmas (Paris Diderot University)
Growing evidence suggests that components of the innate immune system play a crucial role in regulating metabolic homeostasis. Macrophages were the primary immune cells to be described in both the white adipose tissue and the pancreatic islets. Therein, their functions, beneficial or detrimental, are extending under steady state and in the context of obesity-induced type 2 diabetes. Other populations, including innate lymphoid cells, are emerging as key sentinels of metabolic tissues and privile...
Published on Apr 15, 2019in Seminars in Immunopathology 6.80
Marianne Böni-Schnetzler21
Estimated H-index: 21
(University Hospital of Basel),
Daniel T. Meier (University Hospital of Basel)
Metabolic diseases including type 2 diabetes are associated with meta-inflammation. β-Cell failure is a major component of the pathogenesis of type 2 diabetes. It is now well established that increased numbers of innate immune cells, cytokines, and chemokines have detrimental effects on islets in these chronic conditions. Recently, evidence emerged which points to initially adaptive and restorative functions of inflammatory factors and immune cells in metabolism. In the following review, we prov...
Published on May 1, 2019in Molecular metabolism 6.18
F Gerst8
Estimated H-index: 8
(University of Tübingen),
Robert Wagner15
Estimated H-index: 15
(University of Tübingen)
+ 6 AuthorsSusanne Ullrich20
Estimated H-index: 20
(University of Tübingen)
Abstract Background It is now generally accepted that obesity is a major risk factor for type 2 diabetes mellitus (T2DM). Hepatic steatosis in particular, as well as visceral and ectopic fat accumulation within tissues, is associated with the development of the disease. We recently presented the first study on isolated human pancreatic adipocytes and their interaction with islets [Gerst, F., Wagner, R., Kaiser, G., Panse, M., Heni, M., Machann, J., et al., 2017. Metabolic crosstalk between fatty...
Published on Dec 1, 2019in Journal of Neuroinflammation 5.70
Pu Hong (Southern Medical University), Ruo-Nan Gu1
Estimated H-index: 1
(Southern Medical University)
+ 4 AuthorsHong-Fei Zhang2
Estimated H-index: 2
(Southern Medical University)
The NLRP3 (nucleotide-binding oligomerization domain-like receptor [NLR] family pyrin domain-containing 3) inflammasome is a member of the NLR family of innate immune cell sensors. These are crucial regulators of cytokine secretions, which promote ischemic cell death and insulin resistance. This review summarizes recent progress regarding the NLRP3 inflammasome as a potential treatment for ischemic stroke in patients with diabetes, two complicated diseases that often occur together. Stroke worse...