Fig. 8. Schematic illustration of the mechanism for SPINT1-regulated insulin synthesis.

The serine protease inhibitor SPINT1 upholds MAFA-dependent insulin production by targeting the serine protease HEPSIN. Without SPINT1, overactivity of HEPSIN leads to proteolytic processing of its membrane substrate, such as GLP1R, suppressing the MAFA-insulin pathway in β cells. SPINT1 can inhibit HEPSIN’s activity in this regard, thereby augmenting MAFA-dependent insulin expression.