The Role Of Islet Amyloid Polypeptide In Type 2 Diabetes

Islet amyloid polypeptide (IAPP) is co-secreted with insulin from the pancreatic ?-cells. The hormone is involved in glycaemic control, promotion of satiety, and gastric emptying. IAPP amyloid deposits are present in the overwhelming majority of patients with type 2 diabetes, though their role in the pathogenesis of the disease is not fully understood. This report aims to assess the extent to which IAPP aggregates contribute to the loss of ?-cell function in the disease. The development of overt type 2 diabetes is characterised by a shift from a hyperglycaemic state with compensatory hyper-secretion of insulin, to one of pancreatic failure and inability to meet glucose challenge. ?-cell dysfunction is the cause of this change, and its aetiology is complex and multifactorial. IAPP deposits induce ?-cell dysfunction and apoptosis through a variety of intracellular events and apoptotic pathways, disruption of membrane permeability, and through localised inflammation. The formation of IAPP amyloid is poorly understood in vivo, though impaired proIAPP processing and subsequent interaction with perlacans may be one mechanism. IAPP is not the only factor in the pathogenesis of type 2 diabetes but it plays an important role. More research is needed to establish precise toxic pathways and reasons for aggregation in vivo.

Lay Abstract

Islet amyloid polypeptide (IAPP) is a hormone involved in the control of blood sugar levels, the feeling of being full after a meal, and the speed at which the stomach empties. In type 2 diabetes, IAPP forms 'amyloids' (toxic deposits of protein) around the ?-cells of the pancreas, the cells responsible for its production. This report aims to assess whether these amyloids play a role in causing type 2 diabetes by inducing the death of ?-cells. The development of type 2 diabetes can be described as a change from a state where blood sugar levels are high but the ?-cells can still control them, to one where the ?-cells fail. There are multiple causes for this failure of the ?-cells. Amyloids formed from IAPP can cause dysfunction and death of the ?-cells by causing damage to the cell walls, inflammation in the area, and by stimulating molecules that cause the cells to die. The reason behind the formation of these amyloids is poorly understood, but problems in manufacturing IAPP are likely to play a role. IAPP is not the only cause of type 2 diabetes, but it is important alongside others. More research is needed to establish how amyloid formation occurs and how it is dangerous.