Islet amyloid polypeptide aggregation exerts cytotoxic and proinflammatory effects on the islet vasculature in mice – published online 25/07/2022

Joseph J. Castillo, Alfred C. Aplin, Daryl J. Hackney, Meghan F. Hogan, Nathalie Esser, Andrew T. Templin, Rehana Akter, Steven E. Kahn, Daniel P. Raleigh, Sakeneh Zraika, Rebecca L. Hull

Aggregation of islet amyloid polypeptide (IAPP) is a pathologic feature of several forms of diabetes, including type 2 diabetes. Aggregated IAPP accumulates in the islet extracellular matrix between beta cells and the islet vasculature and is well known to be cytotoxic to islet beta cells. However, whether IAPP aggregation is also detrimental to the islet vasculature, an important modulator of beta cell function/survival, has not previously been examined. In this issue, Castillo et al (https://doi.org/10.1007/s00125-022-05756-9) use cell- and animal models to show that IAPP elicits a cytotoxic and pro-inflammatory response from cultured islet microvascular endothelial cells. In pancreases from transgenic mice, the authors found that aggregated IAPP (amyloid deposits) exerts specific, localised effects to increase capillary diameter and increase the number of neuron-glial antigen 2 (NG2)-positive islet pericytal structures. The authors conclude that, together, these findings demonstrate that the islet vasculature is a target of the cytotoxic and proinflammatory effects of IAPP, which is likely to contribute to beta cell failure in diabetes.

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