Extensive amyloid formation in transplanted microencapsulated mouse and human islets

Objective: Deposition of cell toxic islet amyloid is a frequent finding in type 2 diabetes and also in transplanted human islets, where it is a possible explanation for their long-term failure. One suggested reason for amyloid in transplanted islets is that their low vascular density results in a disturbed local clearance of islet amyloid polypeptide (IAPP). To test this hypothesis we analysed accumulation of amyloid in microencapsulated islets, which exemplify a non-vascularised islet graft. Methods: Isolated islets from human or transgenic mice expressing human IAPP were microencapsulated in alginate and cultured in vitro or transplanted under the kidney capsule of normoglycemic nude mice. The degree of amyloid was determined after Congo red staining and subcellular alterations were analysed with electron microscopy. Results: Insulin and IAPP secretion from transgenic mouse islets were markedly increased during stimulation with glucose after one week of culture, but encapsulated islets in general released less insulin. Amyloid was detected after both one and three weeks of culture in the transgenic mouse islets and the encapsulated islets were most affected. After transplantation, electron microscopy displayed both intra-and extracellular amyloid in microencapsulated as well as in non-encapsulated human and transgenic mouse islet grafts. However, amyloid was more frequent in the encapsulated grafts. Conclusion: Micro-encapsulation of pancreatic islets might serve as an important tool for studies of amyloid formation under enhanced circumstances.