Results from this study show that hyperglycaemia and hyperlipidaemia in humans and rat insulin‐producing cells (INS‐1) lead to: (1) an up‐regulation of LD‐associated protein PLIN2, (2) a significant decrease in TFEB activity and in lysosomal biomarker LAMP2, consistent with inhibition of autophagy and (3) dysregulation of genes implicated in lipid metabolism, mitochondrial function and cell survival. Here, PLIN2 is linked to Hyperglycemia.