IDENTIFICATION OF NATURALLY OCCURING IAPP PEPTIDES CAPABLE OF INHIBITING FORMATION OF TOXIC HUMAN IAPP AMYLOID

ABSTRACT 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. 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. Humans are not the only organisms expressing amyloidogenic IAPP, as many organisms are known to express IAPP variants that form toxic amyloid. In general, organisms expressing amyloidogenic IAPP variants have the potential to develop type 2 diabetes-like diseases, while organisms expressing non-amyloidogenic IAPP variants are typically resistant to the disease. In this report, non-human IAPP variants are incubated with hIAPP to identify those variants capable of inhibiting hIAPP aggregation. While most IAPP variants show little ability to interact with hIAPP, several organismal IAPP variants appear to be potent inhibitors of hIAPP aggregation. This proposal strives to identify more organismal IAPP variants with potent hIAPP aggregation inhibition. These variants inhibit hIAPP fibril formation and protect living cells from toxic hIAPP amyloid. Keywords: Amylin, Islet Amyloid Polypeptide, amyloid inhibition, diabete