Iapp-flox Mouse

Iapp, also known as Islet Amyloid Polypeptide or amylin, is a 37-amino-acid pancreatic β-cell hormone. It activates specific multisubunit G protein-coupled receptors, and its major role is as a glucoregulatory hormone, being an important regulator of energy metabolism [2].

In type 2 diabetes, Iapp forms cytotoxic oligomers and amyloid fibrils in islets. These aggregates are toxic to β-cells, inducing β-cell death, dysfunction, and islet inflammation. In transgenic rodents overexpressing human Iapp (hIapp), intracellular pro-apoptotic signals can be generated, indicating that defects in intracellular handling of hIapp can induce cytotoxicity [1]. Also, in mice, overexpression of soluble rodent or oligomer-prone human Iapp induced changes in the islet transcriptome similar to those in prediabetes and type 2 diabetes in humans, including decreased expression of genes conferring β-cell identity and induction of islet inflammation [3].

In conclusion, Iapp is crucial for glucose metabolism and energy regulation. Studies using transgenic rodent models, especially those overexpressing hIapp, have revealed its role in β-cell cytotoxicity, islet inflammation, and the development of type 2 diabetes. Understanding Iapp's function provides insights into the pathophysiology of diabetes and potential therapeutic targets.