title: Ghrelin counteracts insulin-induced activation of vagal afferent neurons via growth hormone secretagogue receptor.
abstract: Vagal afferent nerves sense meal-related gastrointestinal and pancreatic hormones and convey their information to the brain, thereby regulating brain functions including feeding. We have recently demonstrated that postprandial insulin directly acts on the vagal afferent neurons. Plasma concentrations of orexigenic ghrelin and anorexigenic insulin show reciprocal dynamics before and after meals. The present study examined interactive effects of ghrelin and insulin on vagal afferent nerves. Cytosolic Ca(2+) concentration ([Ca(2+)]i) in isolated nodose ganglion (NG) neurons was measured to monitor their activity. Insulin at 10(-7)M increased [Ca(2+)]i in NG neurons, and the insulin-induced [Ca(2+)]i increase was inhibited by treatment with ghrelin at 10(-8)M. This inhibitory effect of ghrelin was attenuated by [D-Lys(3)]-GHRP-6, an antagonist of growth hormone-secretagogue receptor (GHSR). Des-acyl ghrelin had little effect on insulin-induced [Ca(2+)]i increases in NG neurons. Ghrelin did not affect [Ca(2+)]i increases in response to cholecystokinin (CCK), a hormone that inhibits feeding via vagal afferent neurons, indicating that ghrelin selectively counteracts the insulin action. These results demonstrate that ghrelin via GHSR suppresses insulin-induced activation of NG neurons. The action of ghrelin to counteract insulin effects on NG might serve to efficiently inform the brain of the systemic change between fasting-associated ghrelin-dominant and fed-associated insulin-dominant states for the homeostatic central regulation of feeding and metabolism.
authors.affiliation: Division of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.
authors.forename: Yusaku
authors.initials: Y
authors.lastname: Iwasaki
authors.affiliation: Division of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Dezaki
authors.affiliation: Division of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.
authors.forename: Parmila
authors.initials: P
authors.lastname: Kumari
authors.affiliation: First Department of Medicine, Saitama Medical Center, Jichi Medical University School of Medicine, Omiya 1-847, Saitama 330-8503, 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 329-0498, 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; D002118:Calcium / Q000378:metabolism; D054439:Ghrelin / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D008813:Mice, Inbred ICR; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D009620:Nodose Ganglion / Q000187:drug effects / Q000378:metabolism*; D054440:Receptors, Ghrelin / Q000378:metabolism*
chemical_list: D054439:Ghrelin; D007328:Insulin; D054440:Receptors, Ghrelin; D002118:Calcium
keywords: Cholecystokinin; Cytosolic Ca(2+); Feeding; Ghrelin; Growth hormone secretagogue receptor; Insulin; Nodose ganglion; Vagal afferent nerves