Almaça Joana, Molina Judith, Arrojo E Drigo Rafael, Abdulreda Midhat H, Jeon Won Bae, Berggren Per-Olof, Caicedo Alejandro, Nam Hong Gil
Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL 33136; Center for Plant Aging Research, Institute for Basic Science, and Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology, Daegu 711-873, Republic of Korea; Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33136;
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33136;
Proc Natl Acad Sci U S A. 2014 Dec 9;111(49):17612-7. doi: 10.1073/pnas.1414053111. Epub 2014 Nov 17.
Pancreatic islets secrete hormones that play a key role in regulating blood glucose levels (glycemia). Age-dependent impairment of islet function and concomitant dysregulation of glycemia are major health threats in aged populations. However, the major causes of the age-dependent decline of islet function are still disputed. Here we demonstrate that aging of pancreatic islets in mice and humans is notably associated with inflammation and fibrosis of islet blood vessels but does not affect glucose sensing and the insulin secretory capacity of islet beta cells. Accordingly, when transplanted into the anterior chamber of the eye of young mice with diabetes, islets from old mice are revascularized with healthy blood vessels, show strong islet cell proliferation, and fully restore control of glycemia. Our results indicate that beta cell function does not decline with age and suggest that islet function is threatened by an age-dependent impairment of islet vascular function. Strategies to mitigate age-dependent dysregulation in glycemia should therefore target systemic and/or local inflammation and fibrosis of the aged islet vasculature.
胰岛分泌的激素在调节血糖水平（血糖症）中起关键作用。胰岛功能的年龄依赖性损害以及随之而来的血糖调节异常是老年人群面临的主要健康威胁。然而，胰岛功能随年龄下降的主要原因仍存在争议。在此，我们证明小鼠和人类胰岛的衰老与胰岛血管的炎症和纤维化显著相关，但不影响葡萄糖感知和胰岛β细胞的胰岛素分泌能力。因此，当将老年小鼠的胰岛移植到患有糖尿病的年轻小鼠的眼前房时，这些胰岛会通过健康血管实现血管再生，显示出强烈的胰岛细胞增殖，并完全恢复血糖控制。我们的结果表明β细胞功能不会随年龄下降，并提示胰岛功能受到胰岛血管功能的年龄依赖性损害的威胁。因此，减轻血糖年龄依赖性调节异常的策略应针对老年胰岛血管系统的全身性和/或局部炎症及纤维化。
