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Science 322 (5905): 1250-1254

Copyright © 2008 by the American Association for the Advancement of Science

Regulation of Pancreatic β Cell Mass by Neuronal Signals from the Liver

Junta Imai,1 Hideki Katagiri,2* Tetsuya Yamada,1 Yasushi Ishigaki,1 Toshinobu Suzuki,1,2 Hirohito Kudo,1,2 Kenji Uno,2 Yutaka Hasegawa,1 Junhong Gao,2 Keizo Kaneko,1,2 Hisamitsu Ishihara,1 Akira Niijima,3 Masamitsu Nakazato,4 Tomoichiro Asano,5 Yasuhiko Minokoshi,6 Yoshitomo Oka1

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 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.

1 Division of Molecular Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
2 Division of Advanced Therapeutics for Metabolic Diseases, Center for Translational and Advanced Animal Research, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
3 Niigata University School of Medicine, Niigata 951-8150, Japan.
4 Third Department of Internal Medicine, Miyazaki Medical College, University of Miyazaki, Kiyotake, Miyazaki 889-1692, Japan.
5 Department of Medical Science, Graduate School of Medicine, University of Hiroshima, Hiroshima, Japan.
6 Division of Endocrinology and Metabolism, Department of Developmental Physiology, National Institute for Physiological Sciences, Okazaki, Japan.

* To whom correspondence should be addressed. E-mail: katagiri{at}

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