Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 21 November 2008:
Vol. 322. no. 5905, pp. 1250 - 1254
DOI: 10.1126/science.1163971
Prev | Table of Contents | Next

Reports

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

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}mail.tains.tohoku.ac.jp

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Atrial Natriuretic Peptide Promotes Pancreatic Islet {beta}-Cell Growth and Akt/Foxo1a/Cyclin D2 Signaling.
H. You and S. G. Laychock (2009)
Endocrinology 150, 5455-5465
   Abstract »    Full Text »    PDF »
The Transcriptional Response of the Islet to Pregnancy in Mice.
S. Rieck, P. White, J. Schug, A. J. Fox, O. Smirnova, N. Gao, R. K. Gupta, Z. V. Wang, P. E. Scherer, M. P. Keller, et al. (2009)
Mol. Endocrinol. 23, 1702-1712
   Abstract »    Full Text »    PDF »
Minireview: Meeting the Demand for Insulin: Molecular Mechanisms of Adaptive Postnatal ss-Cell Mass Expansion.
M. M. Sachdeva and D. A. Stoffers (2009)
Mol. Endocrinol. 23, 747-758
   Abstract »    Full Text »    PDF »
Role of the liver in glucose homeostasis in PI 3-kinase p85{alpha}-deficient mice.
K. Aoki, J. Matsui, N. Kubota, H. Nakajima, K. Iwamoto, I. Takamoto, Y. Tsuji, A. Ohno, S. Mori, K. Tokuyama, et al. (2009)
Am J Physiol Endocrinol Metab 296, E842-E853
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)