Possible Transmission Route for IAPP and Amyloid Cell-Cell Transfer

Beta-cells produce the two hormones, insulin and IAPP, that regulate blood glucose levels. During the development of type 2 diabetes (T2D), beta-cells are stressed to produce increased amounts of hormones, resulting in dysfunctional cell function and beta-cell death. The hormone IAPP modulates insulin release but is more known for its high propensity to form islet amyloid. Amyloid comprises proteins aggregated into higly ordered fibrilar structures and deposited in one or more organs. IAPP forms amyloid in almost all individuals with T2D, and the amyloid deposits are present in and around beta-cells and cause beta-cell death.

In the last few years, scientists have tried to unravel the mechanism of formation and aggregation of IAPP and its effect on pancreatic beta-cells.

Studies on IAPP amyloid show that in the beginning, amyloid is present in multiple spots in an islet, and when the amyloid mass grows, all beta-cells will be replaced by IAPP amyloid. This pattern raises the question of whether IAPP amyloid starts at multiple sites or if amyloid formed in one cell can be transferred to an adjacent beta-cell.

In this study, IAPP and IAPP amyloid transfer were studied using co-culture of amyloid-containing human islets and fluorescent acceptor cells, Bimolecular fluorescent complementation (BiFC) was used to produce GFP labelled IAPP/Ab amyloid, and IAPP amyloid formation and spreading was monitored in real-time using a Lumascope.  

The expression of fluorescent proteins and immune labelling with specific antibodies were used to identify cell populations, and confocal microscopy was used to determine the transfer of IAPP or amyloid between cells.

In the co-culture of human islet and HEK-293 cells, amyloid could be detected in non-beta cells present in close contact with the amyloid-containing cells. This indicates that amyloid was either transferred between cells or endocytosed by the non-beta-cell. In the BiFC system used, the generation of green fluorescence results from the interaction between the amyloid-forming proteins IAPP and AB. An earlier finding was that IAPP and AB expression results in spot-like amyloid deposits. When HEK293 cells were transfected with ALN2+ILC1 vectors, amyloid was formed, and after co-culture with m-Cherry expressing HEK293 cells, the presence of cells with green and red fluorescence could be found. This points to an interaction between the two populations of HEK 293 cells and the transfer that occurred.

            The results support transfer, but further studies that include inhibitors can help to identify the used pathway.