INS and type 2 diabetes mellitus: Focusing on T2D, recent studies have shown that defects in proinsulin/insulin processing and ER stress markers progressively worsen during the transition from normal glucose tolerance to impaired glucose tolerance, increased expression of ER stress-related genes and increased in β-cell workload (high insulin demand and insulin resistance) that consequently leads to loss of β-cell dysfunction ultimately leading to T2D (48).