title: Glucose-dependent insulinotropic peptide secretion is induced by inflammatory stimuli in an interleukin-1-dependent manner in mice.
abstract: Recently, glucagon-like peptide-1 (GLP-1) levels have been found to be increased in response to inflammatory stimuli, leading to insulin secretion and prevention of hyperglycaemia during endotoxemia in mice. In the present study, we assess the relevance of the other incretin hormone, glucose-dependent insulinotropic peptide (GIP), as a regulator of glucose metabolism under inflammatory conditions. We found that lipopolysaccharide (LPS) increased GIP secretion in a time- and dose-dependent manner in C57BL/6J mice. To elucidate the underlying mechanisms, mice were injected with inflammatory cytokines known to be released by LPS. Circulating GIP levels significantly increased in response to interleukin (IL)-1β but not IL-6 or tumour necrosis factor (TNF)-α administration. Using respective knockout mice we found that LPS-mediated GIP secretion was selectively dependent on IL-1 signalling. To evaluate the functional relevance of inflammatory GIP secretion we pretreated mice with the GIP-receptor antagonist (Pro3)GIP. This blunted LPS-induced TNF-α and IL-6 secretion but did not affect LPS-induced insulin secretion or blood glucose-lowering. In conclusion, GIP provides a novel link between the immune system and the gut, with proinflammatory-immune modulatory function but minor glucose regulatory relevance in the context of acute endotoxemia.
authors.affiliation: Department of Internal Medicine I-Cardiology, University Hospital Aachen, Aachen, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Kahles
authors.affiliation: Department of Internal Medicine I-Cardiology, University Hospital Aachen, Aachen, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Meyer
authors.affiliation: Department of Internal Medicine I-Cardiology, University Hospital Aachen, Aachen, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Diebold
authors.affiliation: Department of Medical Statistics, University Hospital Aachen, Aachen, Germany.
authors.forename: A C
authors.initials: AC
authors.lastname: Foldenauer
authors.affiliation: Department of Internal Medicine I-Cardiology, University Hospital Aachen, Aachen, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Stöhr
authors.affiliation: Department of Internal Medicine I-Cardiology, University Hospital Aachen, Aachen, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Möllmann
authors.affiliation: Department of Internal Medicine I-Cardiology, University Hospital Aachen, Aachen, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Lebherz
authors.affiliation: Department of Cardiology and Angiology, University Hospital Muenster, Muenster, Germany.
authors.forename: H M
authors.initials: HM
authors.lastname: Findeisen
authors.affiliation: Department of Internal Medicine I-Cardiology, University Hospital Aachen, Aachen, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Marx
authors.affiliation: Department of Internal Medicine I-Cardiology, University Hospital Aachen, Aachen, Germany. mlehrke@ukaachen.de.
authors.forename: M
authors.initials: M
authors.lastname: Lehrke
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced* / Q000378:metabolism; D053583:Interleukin-1beta / Q000502:physiology*; D015850:Interleukin-6 / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053573:Receptors, Interleukin-1 Type I / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D001786:Blood Glucose; C583355:IL1R1 protein, mouse; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D053573:Receptors, Interleukin-1 Type I; D005749:Gastric Inhibitory Polypeptide
keywords: 
  GIP
  ; 
  GLP-1; 
  IL-1; 
  IL-6; cytokine; endotoxemia; glucose; incretin; insulin; sepsis