Islet amyloid deposits preferentially in the highly functional and most blood-perfused islets

• Main Authors: Sara Ullsten, Sara Bohman, Marie E Oskarsson, K Peter R Nilsson, Gunilla T Westermark, Per-Ola Carlsson
• Format: Article
• Language: English
• Published: Bioscientifica 2017-09-01
• Series: Endocrine Connections
• Subjects: islet amyloid; pancreatic islets; heterogeneity; blood flow
• Online Access: http://www.endocrineconnections.com/content/6/7/458.full

Islet amyloid and beta cell death in type 2 diabetes are heterogeneous events, where some islets are affected early in the disease process, whereas others remain visibly unaffected. This study investigated the possibility that inter-islet functional and vascular differences may explain the propensity for amyloid accumulation in certain islets. Highly blood-perfused islets were identified by microspheres in human islet amyloid polypeptide expressing mice fed a high-fat diet for three or 10 months. These highly blood-perfused islets had better glucose-stimulated insulin secretion capacity than other islets and developed more amyloid deposits after 10 months of high-fat diet. Similarly, human islets with a superior release capacity formed more amyloid in high glucose culture than islets with a lower release capacity. The amyloid formation in mouse islets was associated with a higher amount of prohormone convertase 1/3 and with a decreased expression of its inhibitor proSAAS when compared to islets with less amyloid. In contrast, levels of prohormone convertase 2 and expression of its inhibitor neuroendocrine protein 7B2 were unaltered. A misbalance in prohormone convertase levels may interrupt the normal processing of islet amyloid polypeptide and induce amyloid formation. Preferential amyloid load in the most blood-perfused and functional islets may accelerate the progression of type 2 diabetes.