Aggregates of islet amyloid polypeptide (IAPP), which are cytotoxic, occur in type 2 diabetes. These lesions are heterogeneous, leading to inconsistencies in β-cell death between islets or between different parts of the pancreas. This is in line with the heterogeneous nature of pancreatic islets including differences in blood supply, which the authors previously described; low blood supply results in islets with dormant metabolic activity, whilst islets with increased blood supply exhibit raised glucose-stimulated insulin secretion.

Since IAPP is co-secreted with insulin, and increased IAPP production and secretion trigger aggregate formation, Ullsten et al. sought to determine whether a subpopulation of highly perfused islets would be more predisposed to amyloid formation. They used human IAPP-expressing mice fed a high fat diet and adopted a microsphere technique to identify highly blood-perfused, highly functional islets. The authors found preferential amyloid development in these islets, along with 30% higher glucose-stimulated insulin secretion.

These findings suggest that, although islets can increase insulin secretion to compensate for raised insulin resistance, this may inadvertently lead to increased amyloid aggregates in these islets, thus accelerating the progression of type 2 diabetes.

Read the full article in Endocrine Connections 6 458–468.