Molecular Effects of hIAPP on Pancreatic β‐cells

Abstract

A common pathological feature of Type II diabetes is the presence of islet amyloid polypeptide (IAPP) aggregates in the pancreatic beta cells. These aggregates are a possible explanation for the death of beta cells in diabetes patients. The purpose of this study is to determine if human IAPP (hIAPP) is toxic to β-cells and investigate possible mechanisms for its toxicity. Cell viability and cytotoxicity assays along with cell imaging and RNA- seq data were used to determine the effects of hIAPP on pancreatic β-cells. Results show that the addition of increasing amounts of hIAPP led to decreased cell viability. Cytotoxicity assay indicated membrane damage, while cell imaging showed changes in the morphology of cells as a result of hIAPP. RNA-seq analysis revealed differentially expressed genes related to cellular stress and the UPR system. These results suggest that hIAPP is toxic to cells and is damaging to the cell membrane. Further analysis is necessary to determine the molecular mechanism of hIAPP toxicity.