title: Postprandial macrophage-derived IL-1β stimulates insulin, and both synergistically promote glucose disposal and inflammation.
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.
authors.affiliation: Clinic of Endocrinology, Diabetes and Metabolism University Hospital Basel, Basel, Switzerland, and Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Erez
authors.initials: E
authors.lastname: Dror
authors.affiliation: Clinic of Endocrinology, Diabetes and Metabolism University Hospital Basel, Basel, Switzerland, and Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Elise
authors.initials: E
authors.lastname: Dalmas
authors.affiliation: Clinic of Endocrinology, Diabetes and Metabolism University Hospital Basel, Basel, Switzerland, and Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Meier
authors.affiliation: Deptartment of Pediatric Endocrinology and Diabetology and Children's Research Center, University Children's Hospital, Zurich, Switzerland.
authors.forename: Stephan
authors.initials: S
authors.lastname: Wueest
authors.affiliation: Inserm, University Lille, Centre Hospitalier Universitaire, Lille, France, and Translational Research for Diabetes, European Genomic Institute for Diabetes, Lille, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Thévenet
authors.affiliation: Clinic of Endocrinology, Diabetes and Metabolism University Hospital Basel, Basel, Switzerland, and Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Constanze
authors.initials: C
authors.lastname: Thienel
authors.affiliation: Clinic of Endocrinology, Diabetes and Metabolism University Hospital Basel, Basel, Switzerland, and Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Katharina
authors.initials: K
authors.lastname: Timper
authors.affiliation: Clinic of Endocrinology, Diabetes and Metabolism University Hospital Basel, Basel, Switzerland, and Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Thierry M
authors.initials: TM
authors.lastname: Nordmann
authors.affiliation: Clinic of Endocrinology, Diabetes and Metabolism University Hospital Basel, Basel, Switzerland, and Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Shuyang
authors.initials: S
authors.lastname: Traub
authors.affiliation: Clinic of Endocrinology, Diabetes and Metabolism University Hospital Basel, Basel, Switzerland, and Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Friederike
authors.initials: F
authors.lastname: Schulze
authors.affiliation: Deptartment of Pediatric Endocrinology and Diabetology and Children's Research Center, University Children's Hospital, Zurich, Switzerland.
authors.forename: Flurin
authors.initials: F
authors.lastname: Item
authors.affiliation: Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Vallois
authors.affiliation: Inserm, University Lille, Centre Hospitalier Universitaire, Lille, France, and Translational Research for Diabetes, European Genomic Institute for Diabetes, Lille, France.
authors.forename: Francois
authors.initials: F
authors.lastname: Pattou
authors.affiliation: Inserm, University Lille, Centre Hospitalier Universitaire, Lille, France, and Translational Research for Diabetes, European Genomic Institute for Diabetes, Lille, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Kerr-Conte
authors.affiliation: Cell Isolation and Transplantation Center, Department of Surgery, Geneva University Hospitals, Geneva, Switzerland, and University of Geneva School of Medicine, Geneva, Switzerland.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Lavallard
authors.affiliation: Cell Isolation and Transplantation Center, Department of Surgery, Geneva University Hospitals, Geneva, Switzerland, and University of Geneva School of Medicine, Geneva, Switzerland.
authors.forename: Thierry
authors.initials: T
authors.lastname: Berney
authors.affiliation: Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
authors.forename: Bernard
authors.initials: B
authors.lastname: Thorens
authors.affiliation: Deptartment of Pediatric Endocrinology and Diabetology and Children's Research Center, University Children's Hospital, Zurich, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Konrad
authors.affiliation: Clinic of Endocrinology, Diabetes and Metabolism University Hospital Basel, Basel, Switzerland, and Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Marianne
authors.initials: M
authors.lastname: Böni-Schnetzler
authors.affiliation: Clinic of Endocrinology, Diabetes and Metabolism University Hospital Basel, Basel, Switzerland, and Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Marc Y
authors.initials: MY
authors.lastname: Donath
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism; D007249:Inflammation / Q000276:immunology*; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000502:physiology*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism; D019518:Postprandial Period; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism
chemical_list: D058847:Inflammasomes; D007328:Insulin; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D017382:Reactive Oxygen Species; C490299:Slc5a2 protein, mouse; D051297:Sodium-Glucose Transporter 2; D005947:Glucose