IAPP and Hyperglycemia: Elevated blood glucose triggers hyperglucotoxicity, leading to aggravation of IR and deterioration of β cell function, creating a vicious cycle that leads to further elevation of blood glucose to diabetic levels and even hyperglycemic crises.164 In addition, hyperglycemia and other metabolic disorders such as dyslipidemia, inflammatory factors, excess IAPP and alterations in the gut microbiota, combine to contribute to IR and/or β cell dysfunction through the common pathways of inflammation, ERS and oxidative stress (Fig. 3).