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Science 309 (5744): 2232-2234

Copyright © 2005 by the American Association for the Advancement of Science

IP3 Receptor Types 2 and 3 Mediate Exocrine Secretion Underlying Energy Metabolism

Akira Futatsugi,1,2* Takeshi Nakamura,1,3 Maki K. Yamada,3 Etsuko Ebisui,1,2 Kyoko Nakamura,1,3 Keiko Uchida,3 Tetsuya Kitaguchi,2 Hiromi Takahashi-Iwanaga,4 Tetsuo Noda,5 Jun Aruga,2 Katsuhiko Mikoshiba1,2,3*

Abstract: Type 2 and type 3 inositol 1,4,5-trisphosphate receptors (IP3R2 and IP3R3) are intracellular calcium-release channels whose physiological roles are unknown. We show exocrine dysfunction in IP3R2 and IP3R3 double knock-out mice, which caused difficulties in nutrient digestion. Severely impaired calcium signaling in acinar cells of the salivary glands and the pancreas in the double mutants ascribed the secretion deficits to a lack of intracellular calcium release. Despite a normal caloric intake, the double mutants were hypoglycemic and lean. These results reveal IP3R2 and IP3R3 as key molecules in exocrine physiology underlying energy metabolism and animal growth.

1 Calcium Oscillation, International Cooperative Research Project, Japan Science and Technology Agency, Tokyo 108-0071, Japan.
2 Laboratory for Developmental Neurobiology, Brain Development Research Group, Brain Science Institute, RIKEN, Saitama 351-0198, Japan.
3 Division of Molecular Neurobiology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
4 Department of Anatomy, School of Medicine, Hokkaido University, Sapporo 060-8638, Japan.
5 Department of Cell Biology, Japanese Foundation for Cancer Research, Cancer Institute, Tokyo 170-8455, Japan.

* To whom correspondence should be addressed. E-mail: afutatsu{at}brain.riken.jp (A.F.); mikosiba{at}ims.u-tokyo.ac.jp (K.M.)

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