Regulation of pancreatic β cell mass by neuronal signals from the liver

Junta Imai, Hideki Katagiri, Tetsuya Yamada, Yasushi Ishigaki, Toshinobu Suzuki, Hirohito Kudo, Kenji Uno, Yutaka Hasegawa, Junhong Gao, Keizo Kaneko, Hisamitsu Ishihara, Akira Niijima, Masamitsu Nakazato, Tomoichiro Asano, Yasuhiko Minokoshi, Yoshitomo Oka

Research output: Contribution to journalArticlepeer-review

188 Citations (Scopus)


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 β cell mass, pathophysiological compensation for insulin resistance. We found that hepatic activation of extracellular regulated kinase (ERK) signaling induced pancreatic β 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 β cell mass and normalized serum glucose levels. Thus, interorgan metabolic relay systems may serve as valuable targets in regenerative treatments for diabetes.

Original languageEnglish
Pages (from-to)1250-1254
Number of pages5
Issue number5905
Publication statusPublished - 2008 Nov 21


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