Islet amyloid inhibitors improve glucose homeostasis in a transgenic mouse model of type 2 diabetes

Increasing evidence points to the cytotoxicity of islet amyloid polypeptide ( IAPP ) aggregates as a major contributor to the loss of β‐cell mass in type 2 diabetes. Prevention of IAPP formation represents a potential treatment to increase β‐cell survival and function. The IAPP inhibitory peptide, D‐ANFLVH , has been previously shown to prevent islet amyloid accumulation in cultured human islets. To assess its activity in vivo , D‐ANFLVH was administered by intraperitoneal injection into a human IAPP transgenic mouse model, which replicates type 2 diabetes islet amyloid pathology. The peptide was a potent inhibitor of islet amyloid deposition, resulting in reduced islet cell apoptosis and preservation of β‐cell area leading to improved glucose tolerance. These findings provide support for a key role of islet amyloid in β‐cell survival and validate the application of anti‐amyloid compounds as therapeutic strategies to maintain normal insulin secretion in patients with type 2 diabetes.