Several reports support the existence of K-ATP–channel and L-type calcium channel–containing (LTCC-containing) Ca2+ microdomains, or hotspots, in the plasma membrane of neuroendocrine cells, with channels preassembled with docked insulin granules, resulting in rapid exocytosis synchronized with membrane depolarization, a process disturbed in T2D (78). This evidence concerns the gene INS and type 2 diabetes mellitus.