The Role of Human IAPP in Stress and Inflammatory Processes in Type 2 Diabetes

Abstract

Understanding the mechanisms regulating whole-body glucose homeostasis is important in order to understand what happens in a disease such as type 2 diabetes (T2D). Insulin resistance, inflammation, dysfunction of islet β-cells, and the presence of amyloid deposits in the pancreas are some of the major causes involved in the process of β-cell deterioration. The unique peptide constituent of amyloid deposits, human islet amyloid polypeptide (hIAPP), is capable of inducing endoplasmic reticulum (ER) stress and the resulting unfolded-protein response activation. Additionally, hIAPP has been shown to induce interleukin-1β expression, the main cytokine involved in inflamma‐ tion and T2D causing inflammation and eventually, inducing apoptosis. Nevertheless, the mechanisms behind the process of hIAPP aggregation and amyloid formation are still unknown. In this chapter, we describe the different mechanisms by which hIAPP induces ER stress and inflammation. This should open the door for designing therapeutic interventions aimed at modulating the immune system and the ER stress response. Keywords: Diabetes, pancreatic amyloid, inflammation, ER stress, IAPP, chaperones, diabetes