title: Glucagon directly interacts with vagal afferent nodose ganglion neurons to induce Ca(2+) signaling via glucagon receptors.
abstract: Glucagon is released from the pancreatic islets postprandially and under hypoglycemic and cold conditions, and regulates glucose metabolism, feeding, energy expenditure and heat production, the functions partly controlled by the brain. Peripheral glucagon could signal to the brain via passing through the blood-brain barrier and/or acting on the vagal afferent. However, the latter remains to be determined. The present study aimed to clarify whether glucagon directly interacts with the nodose ganglion (NG) neurons of vagal afferent nerves in mice. In vivo study showed that intraperitoneal injection of glucagon induced phosphorylation of extracellular signal regulated kinase 1 and 2 (ERK1/2), cellular activation makers, in NG neurons. In fura-2 microfluorometric studies, glucagon increased cytosolic Ca(2+) concentration ([Ca(2+)]i) in single NG neurons. The glucagon-induced [Ca(2+)]i increases were suppressed by a glucagon receptor antagonist, des-His(1)-[Glu(9)]-Glucagon (1-29) amide, and the glucagon receptor mRNA was expressed in NG neurons. The majority of glucagon-responsive NG neurons exhibited [Ca(2+)]i responses to insulin and cholecystokinin-8, the hormones that are secreted postprandially and implicated in satiety. These results demonstrate that glucagon, by interacting with the glucagon receptor, directly activates vagal afferent nerves, possibly being relayed to the signaling to the brain and formation of satiety.
authors.affiliation: Division of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi 320-0498, Japan.
authors.forename: Enkh-Amar
authors.initials: EA
authors.lastname: Ayush
authors.affiliation: Division of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi 320-0498, Japan.
authors.forename: Yusaku
authors.initials: Y
authors.lastname: Iwasaki
authors.affiliation: Division of Human Genetics, Center of Molecular Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 320-0498, Japan.
authors.forename: Sadahiko
authors.initials: S
authors.lastname: Iwamoto
authors.affiliation: Health Science Service Center, Kanazawa University, Kanazawa, Ishikawa 920-1192, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Nakabayashi
authors.affiliation: First Department of Medicine, Saitama Medical Center, Jichi Medical University School of Medicine, Omiya 1-847, Saitama 337-8503, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kakei
authors.affiliation: Division of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi 320-0498, Japan; Division of Adaptation Development, Department of Developmental Physiology, National Institute for Physiological Sciences, Okazaki, Aichi 444-8585, Japan. Electronic address: tyada@jichi.ac.jp.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yada
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D005934:Glucagon / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D007274:Injections, Intraperitoneal; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D009475:Neurons, Afferent / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D009620:Nodose Ganglion / Q000187:drug effects / Q000502:physiology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D018027:Receptors, Glucagon / Q000037:antagonists & inhibitors / Q000502:physiology*; D012528:Satiety Response / Q000187:drug effects / Q000502:physiology*; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*
chemical_list: D018027:Receptors, Glucagon; C080071:glucagonamide, desHis(1)-Glu(9)-; D005934:Glucagon; C540215:Mark3 protein, mouse; D017346:Protein Serine-Threonine Kinases; C535148:Mapk1 protein, mouse; D019950:Mitogen-Activated Protein Kinase 1
keywords: Cholecystokinin; Glucagon; Glucagon receptor; Insulin; Nodose ganglion; Satiety