The molecular basis of islet amyloid induced beta-cell death and the inhibition of islet amyloid induced toxicity

Amyloid-forming proteins are clumping together and killing pancreatic beta cells, and researchers still do not know exactly how or why. This matters because the toxic clumps—called islet amyloid—form from a hormone called IAPP and are a hallmark of type 2 diabetes. Despite decades of research, no one has pinned down the precise mechanism by which these clumps damage cells, nor why some drug candidates that block amyloid formation actually make things worse. The team behind this grant has developed new laboratory tools to tackle four unanswered questions: how IAPP assembles into amyloid, what makes some clumps toxic and others harmless, and why certain inhibitors protect cells while others promote toxicity. This is fundamental science. If successful, it would provide the first detailed molecular understanding of amyloid formation for any protein, not just IAPP. That knowledge could eventually guide the design of drugs that selectively block toxic oligomers without triggering harmful side effects. Similar fundamental work on amyloid proteins in Alzheimer’s and Parkinson’s diseases has already reshaped how researchers think about neurodegeneration; a clearer picture of islet amyloidosis could do the same for diabetes.