Regulation of pancreatic beta cell mass by neuronal signals from the liver.
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.
Imai
Junta
J
Division of Molecular Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
Katagiri
Hideki
H
Yamada
Tetsuya
T
Ishigaki
Yasushi
Y
Suzuki
Toshinobu
T
Kudo
Hirohito
H
Uno
Kenji
K
Hasegawa
Yutaka
Y
Gao
Junhong
J
Kaneko
Keizo
K
Ishihara
Hisamitsu
H
Niijima
Akira
A
Nakazato
Masamitsu
M
Asano
Tomoichiro
T
Minokoshi
Yasuhiko
Y
Oka
Yoshitomo
Y
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
D007328:Insulin; D011994:Recombinant Proteins; D048369:MAP Kinase Kinase 1; C482127:Map2k1 protein, mouse