There is one report on the reuptake of glucagon by α-cells after secretion and trafficking to the endolysosomal system for degradation.19 Interestingly, parallel findings in β-cells showed that there is a shuttling of proinsulin from secretory pathway toward the endolysosomal system for degradation, which may be an underlying mechanism for β-cell failure in type 2 diabetes.20 Therefore, the endolysosomal trafficking may be a novel pathway for the dysregulation of both insulin and glucagon secretion in diabetes. Here, INS is linked to type 2 diabetes mellitus.