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

Science, 21 November 2008
Vol. 322, Issue 5905, p. 1250-1254
DOI: 10.1126/science.1163971

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

  1. Junta Imai1,
  2. Hideki Katagiri2,*,
  3. Tetsuya Yamada1,
  4. Yasushi Ishigaki1,
  5. Toshinobu Suzuki1,2,
  6. Hirohito Kudo1,2,
  7. Kenji Uno2,
  8. Yutaka Hasegawa1,
  9. Junhong Gao2,
  10. Keizo Kaneko1,2,
  11. Hisamitsu Ishihara1,
  12. Akira Niijima3,
  13. Masamitsu Nakazato4,
  14. Tomoichiro Asano5,
  15. Yasuhiko Minokoshi6,
  16. Yoshitomo Oka1
  1. 1 Division of Molecular Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
  2. 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. 3 Niigata University School of Medicine, Niigata 951-8150, Japan.
  4. 4 Third Department of Internal Medicine, Miyazaki Medical College, University of Miyazaki, Kiyotake, Miyazaki 889-1692, Japan.
  5. 5 Department of Medical Science, Graduate School of Medicine, University of Hiroshima, Hiroshima, Japan.
  6. 6 Division of Endocrinology and Metabolism, Department of Developmental Physiology, National Institute for Physiological Sciences, Okazaki, Japan.
  1. * To whom correspondence should be addressed. E-mail: katagiri{at}


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.

  • Received for publication 5 February 2008.
  • Accepted for publication 15 October 2008.


J. Imai, H. Katagiri, T. Yamada, Y. Ishigaki, T. Suzuki, H. Kudo, K. Uno, Y. Hasegawa, J. Gao, K. Kaneko, H. Ishihara, A. Niijima, M. Nakazato, T. Asano, Y. Minokoshi, and Y. Oka, Regulation of Pancreatic β Cell Mass by Neuronal Signals from the Liver. Science 322, 1250-1254 (2008).

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