Human
islet amyloid polypeptide (hIAPP) is the major component of the
amyloid deposits found in the pancreatic islets of patients with
type 2 diabetes mellitus (T2DM). Mature hIAPP, a 37-aa
peptide, is natively unfolded in its monomeric state but forms islet
amyloid in T2DM. In common with other misfolded and aggregated
proteins, amyloid formation involves aggregation of monomers of hIAPP into oligomers, fibrils, and ultimately mature
amyloid deposits. hIAPP is coproduced and stored with
insulin by the pancreatic islet β-cells and is released in response to the stimuli that lead to insulin secretion. Accumulating evidence suggests that hIAPP
amyloid deposits that accompany T2DM are not just an insignificant phenomenon derived from the
disease progression but that hIAPP aggregation induces processes that impair the functionality and the viability of β-cells. In this review, we particularly focus on hIAPP structure, hIAPP aggregation, and hIAPP-membrane interactions. We will also discuss recent findings on the mechanism of hIAPP-membrane damage and on hIAPP-induced cell death. Finally, the development of successful antiamyloidogenic agents that prevent hIAPP fibril formation will be examined.