title: Regulation of pancreatic beta cell mass by neuronal signals from the liver.
abstract: Metabolic regulation in mammals requires communication between multiple organs and tissues. The rise in the incidence of obesity and associated metabolic disorders, including type 2 diabetes, has renewed interest in interorgan communication. We used mouse models to explore the mechanism whereby obesity enhances pancreatic beta cell mass, pathophysiological compensation for insulin resistance. We found that hepatic activation of extracellular regulated kinase (ERK) signaling induced pancreatic beta cell proliferation through a neuronal-mediated relay of metabolic signals. This metabolic relay from the liver to the pancreas is involved in obesity-induced islet expansion. In mouse models of insulin-deficient diabetes, liver-selective activation of ERK signaling increased beta cell mass and normalized serum glucose levels. Thus, interorgan metabolic relay systems may serve as valuable targets in regenerative treatments for diabetes.
authors.affiliation: Division of Molecular Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors.forename: Junta
authors.initials: J
authors.lastname: Imai
authors.forename: Hideki
authors.initials: H
authors.lastname: Katagiri
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yamada
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ishigaki
authors.forename: Toshinobu
authors.initials: T
authors.lastname: Suzuki
authors.forename: Hirohito
authors.initials: H
authors.lastname: Kudo
authors.forename: Kenji
authors.initials: K
authors.lastname: Uno
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Junhong
authors.initials: J
authors.lastname: Gao
authors.forename: Keizo
authors.initials: K
authors.lastname: Kaneko
authors.forename: Hisamitsu
authors.initials: H
authors.lastname: Ishihara
authors.forename: Akira
authors.initials: A
authors.lastname: Niijima
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Nakazato
authors.forename: Tomoichiro
authors.initials: T
authors.lastname: Asano
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Minokoshi
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Oka
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002490:Central Nervous System / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D006965:Hyperplasia; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000378:metabolism*; D048369:MAP Kinase Kinase 1 / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D010179:Pancreas / Q000294:innervation; D011994:Recombinant Proteins / Q000378:metabolism; D014630:Vagus Nerve / Q000166:cytology / Q000378:metabolism; D014981:Xenopus
chemical_list: D007328:Insulin; D011994:Recombinant Proteins; D048369:MAP Kinase Kinase 1; C482127:Map2k1 protein, mouse