In addition, chronic hyperglycemia increases proinsulin biosynthesis and formation of IAPP in the beta cells which leads to accumulation of misfolded IAPP and ROS production, disruption of ER Ca2+ homeostasis, activation of the UPR pathways leading to proinsulin degradation and beta cell death (Haataja et al., 2008; Hasnain et al., 2016). Here, INS is linked to Hyperglycemia.