IP3 receptor types 2 and 3 mediate exocrine secretion underlying energy metabolism

Type 2 and type 3 inositol 1,4,5-trisphosphate receptors (IP3 R2 and IP(3)R3) are intracellular calcium-release channels whose physiological roles are unknown. We show exocrine dysfunction in IP3 R2 and IP3 R3 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 tack of intracellular calcium release. Despite a normal caloric intake, the double mutants were hypoglycemic and lean. These results reveal IP3 R2 and IP3 R3 as key molecules in exocrine physiology underlying energy metabolism and animal growth.