Islet endothelial cells [ECs] produce numerous factors that support normal β-cell function and survival. Under diabetic conditions, islet ECs develop an activated (pro-inflammatory, pro-adhesive) phenotype which contributes to β-cell failure. In human type 2 diabetes [T2D], aggregation of the β-cell product, islet amyloid polypeptide [IAPP], results in amyloid deposition in the islet perivascular space. The toxic effects of IAPP aggregation on the β-cell are well established, however, whether islet ECs are also susceptible to IAPP toxicity remains unknown. We hypothesized that aggregation of amyloidogenic human IAPP (hIAPP) contributes to islet EC activation in T2D. To test this hypothesis, we performed 24h treatments of primary rat islet ECs with hIAPP [0-20 µM] for 24h, along with non-amyloidogenic rat IAPP [rIAPP; 20 µM] as a control, and, subsequently, the MS1 islet EC line with hIAPP [0-20 µM] ± the amyloid inhibitor Congo Red [CR; 100 µM]. In primary islet ECs, hIAPP, but not rIAPP, reduced cell viability and increased activation markers (interleukin-6, endothelin-1, vascular cell adhesion molecule; Table). A similar effect was seen in MS1 cells, and this was abrogated with CR (Table). Our data suggest that islet ECs are susceptible to hIAPP-induced toxicity. The resulting EC activation may interrupt the cross talk between the EC and β-cell, and thereby contribute to the β-cell toxicity of IAPP in T2D.


J.J. Castillo: None. M.F. Hogan: None. A. Aplin: None. D.J. Hackney: None. R.L. Hull: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc.


National Institute of Diabetes and Digestive and Kidney Diseases (R01DK088082); National Heart, Lung, and Blood Institute (T32HL007028); U.S. Department of Veterans Affairs (BX004063)

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