Hyperglycemia can induce ER stress, which is considered a major contributor to hepatic insulin resistance by favouring de novo lipogenesis (leading to hepatic lipid accumulation), and interfering in insulin signalling, in part, through IRE1/c-Jun N-terminal kinase (JNK) pathway activation (leading to hepatic insulin resistance and DM) [14, 65]. Here, INS is linked to Insulin resistance.