IP3 receptor types 2 and 3 mediate exocrine secretion underlying energy metabolism.
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.
Futatsugi
Akira
A
Calcium Oscillation, International Cooperative Research Project, Japan Science and Technology Agency, Tokyo 108-0071, Japan. afutatsu@brain.riken.jp
Nakamura
Takeshi
T
Yamada
Maki K
MK
Ebisui
Etsuko
E
Nakamura
Kyoko
K
Uchida
Keiko
K
Kitaguchi
Tetsuya
T
Takahashi-Iwanaga
Hiromi
H
Noda
Tetsuo
T
Aruga
Jun
J
Mikoshiba
Katsuhiko
K
D000681:Amylases / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000502:physiology*; D020013:Calcium Signaling; D002217:Carbachol / Q000494:pharmacology; D004063:Digestion; D004435:Eating; D002149:Energy Intake; D004734:Energy Metabolism; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008049:Lipase / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D046790:Pancreas, Exocrine / Q000166:cytology / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000502:physiology*; D012463:Saliva / Q000378:metabolism*; D012472:Salivation; D013363:Submandibular Gland / Q000378:metabolism; D014362:Trypsinogen / Q000378:metabolism
D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D002217:Carbachol; D014362:Trypsinogen; D008049:Lipase; D000681:Amylases; D002118:Calcium