MARK2 and congenital isolated hyperinsulinism: In particular, Sirolimus, is an antiproliferative drug that reduces insulin secretion probably by lowering the mammalian target of rapamycin (mTOR), a serine/threonine kinase that is overexpressed in the diffuse variant of CHI and which enhances insulin secretion; moreover, Sirolimus causes depletion of intracellular Calcium decreasing insulin release (48).