Aim: To identify naturally occurring variants of IAPP capable of inhibiting the aggregation
of human IAPP and protecting living cells from the toxic effects of human IAPP.
Background: The loss of insulin-producing β-cells and the overall progression of type 2 diabetes
appears to be linked to the formation of toxic human IAPP (hIAPP, Islet Amyloid Polypeptide,
amylin) amyloid in the pancreas. Inhibiting the initial aggregation of hIAPP has the potential to
slow, if not stop entirely, the loss of β-cells and halt the progression of the disease.
Objective: To identify and characterize naturally occurring variants of IAPP capable of inhibiting
human IAPP aggregation.
Methods: Synthetic human IAPP was incubated with synthetic IAPP variants identified from natural
sources under conditions known to promote amyloid-based aggregation. To identify IAPP
variants capable of inhibiting human IAPP aggregation, Thioflavin T-binding fluorescence, atomic
force microscopy, and cell-rescue assays were performed.
Results: While most IAPP variants showed little to no ability to inhibit human IAPP aggregation,
several variants showed some ability to inhibit aggregation, with two variants showing substantial
Conclusion: Several naturally occurring IAPP variants capable of inhibiting human IAPP aggregation
were identified and characterized.