spint1 specific knokout in mouse pancreas islet SILAC

SPINT1 is a membrane-anchored serine protease inhibitor that modulates pericellular proteolysis. The pancreas-specific disruption of Spint1 in mice significantly decreased islet size and mass, leading to glucose intolerance, which was causally related to the down-regulation of MafA and insulin. Mechanistically, the silencing of Hepsin (encoding a SPINT1 target protease) counteracted the repressive effect of Spint1 knockdown on MafA and Ins1 expression in β cells. Together, the results suggest that SPINT1 plays a novel role in β cells to maintain glucose homeostasis and insulin production.