title: Interleukin-6 amplifies glucagon secretion: coordinated control via the brain and pancreas.
abstract: Inappropriate glucagon secretion contributes to hyperglycemia in inflammatory disease. Previous work implicates the proinflammatory cytokine interleukin-6 (IL-6) in glucagon secretion. IL-6-KO mice have a blunted glucagon response to lipopolysaccharide (LPS) that is restored by intravenous replacement of IL-6. Given that IL-6 has previously been demonstrated to have a transcriptional (i.e., slow) effect on glucagon secretion from islets, we hypothesized that the rapid increase in glucagon following LPS occurred by a faster mechanism, such as by action within the brain. Using chronically catheterized conscious mice, we have demonstrated that central IL-6 stimulates glucagon secretion uniquely in the presence of an accompanying stressor (hypoglycemia or LPS). Contrary to our hypothesis, however, we found that IL-6 amplifies glucagon secretion in two ways; IL-6 not only stimulates glucagon secretion via the brain but also by direct action on islets. Interestingly, IL-6 augments glucagon secretion from both sites only in the presence of an accompanying stressor (such as epinephrine). Given that both adrenergic tone and plasma IL-6 are elevated in multiple inflammatory diseases, the interactions of the IL-6 and catecholaminergic signaling pathways in regulating GCG secretion may contribute to our present understanding of these diseases.
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Tammy M
authors.initials: TM
authors.lastname: Barnes
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Yolanda F
authors.initials: YF
authors.lastname: Otero
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Amicia D
authors.initials: AD
authors.lastname: Elliott
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Alicia D
authors.initials: AD
authors.lastname: Locke
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Malabanan
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Anastasia G
authors.initials: AG
authors.lastname: Coldren
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Marcela
authors.initials: M
authors.lastname: Brissova
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: David W
authors.initials: DW
authors.lastname: Piston
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee owen.mcguinness@vanderbilt.edu.
authors.forename: Owen P
authors.initials: OP
authors.lastname: McGuinness
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004837:Epinephrine / Q000494:pharmacology; D005934:Glucagon / Q000187:drug effects / Q000378:metabolism*; D050416:Glucagon-Secreting Cells / Q000378:metabolism*; D015309:Glucose Clamp Technique; D007003:Hypoglycemia / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013312:Stress, Physiological; D013566:Sympathomimetics / Q000494:pharmacology
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D013566:Sympathomimetics; C577686:interleukin-6, mouse; D005934:Glucagon; D004837:Epinephrine
keywords: endotoxemia; glucagon; hypoglycemia; inflammation; interleukin-6