As such, a prolonged increase in insulin secretory rates have been related to endoplasmic reticulum (ER) stress, depletion of intracellular insulin stores and beta-cell apoptosis.41 Pancreatic islets from individuals with T2D have lower insulin content compared to healthy controls.42 In mice, hyperglycemia leads to insulin content loss.43 Reversibly, strategies that induce beta-cell rest are linked to improved beta-cell function over time.44 Here, INS is linked to Hyperglycemia.