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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amylases / metabolism
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Animals
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Body Weight
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Calcium / metabolism
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Calcium Channels / genetics
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Calcium Channels / physiology*
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Calcium Signaling
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Carbachol / pharmacology
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Digestion
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Eating
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Energy Intake
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Energy Metabolism*
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Inositol 1,4,5-Trisphosphate Receptors
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Lipase / metabolism
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Mice
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Mice, Knockout
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Pancreas, Exocrine / cytology
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Pancreas, Exocrine / metabolism*
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Receptors, Cytoplasmic and Nuclear / genetics
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Receptors, Cytoplasmic and Nuclear / physiology*
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Saliva / metabolism*
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Salivation
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Submandibular Gland / metabolism
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Trypsinogen / metabolism
Substances
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Calcium Channels
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Inositol 1,4,5-Trisphosphate Receptors
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Receptors, Cytoplasmic and Nuclear
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Carbachol
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Trypsinogen
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Lipase
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Amylases
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Calcium