The Molecular Effect of Natural IAPP Variants on Pancreatic Beta Cell Gene Expression

Diabetes is the seventh leading cause of death and it is still likely to be underreported. Pancreatic beta cells, which are responsible for releasing insulin, have been found to undergo apoptosis in this disease, causing an imbalance in glucose reabsorption. Previous research has shown that islet amyloid polypeptide (IAPP), co-secreted with insulin, aggregates in these cells and contributes to their cell death. Therefore, finding inhibitors for this phenomenon is crucial to allow beta cells to live longer and increase survival rate and quality of life for patients with diabetes. We have found several natural IAPP variants that are inhibitors of human IAPP (hIAPP) aggregation. This work focuses on two natural IAPP variants – IAPPvR and IAPPvC.Both variants are capable of inhibiting human IAPP fiber formation and rescue the cells from the toxic effects of hIAPP. RNA seq results were used to identify differentially expressed genes responsible for the rescue. RNA seq data revealed several genes related to the unfolded protein response system and vesicle function. Further analysis is necessary to confirm the molecular mechanism responsible for this cellular response.