Young capillary vessels rejuvenate aged pancreatic islets

被引:80
作者
Almaca, Joana [1 ,2 ,3 ,4 ]
Molina, Judith [4 ]
Arrojo e Drigo, Rafael [4 ,5 ,6 ]
Abdulreda, Midhat H. [1 ]
Jeon, Won Bae [7 ]
Berggren, Per-Olof [1 ,5 ,6 ,8 ]
Caicedo, Alejandro [1 ,4 ,9 ,10 ]
Nam, Hong Gil [2 ,3 ]
机构
[1] Univ Miami, Miller Sch Med, Diabet Res Inst, Miami, FL 33136 USA
[2] Daegu Gyeongbuk Inst Sci & Technol, Inst Basic Sci, Ctr Plant Aging Res, Taegu 711873, South Korea
[3] Daegu Gyeongbuk Inst Sci & Technol, Dept New Biol, Taegu 711873, South Korea
[4] Univ Miami, Miller Sch Med, Dept Med, Div Endocrinol Diabet & Metab, Miami, FL 33136 USA
[5] Nanyang Technol Univ, Lee Kong Chien Sch Med, Singapore, Singapore
[6] Univ London Imperial Coll Sci Technol & Med, London, England
[7] Daegu Gyeongbuk Inst Sci & Technol, Div NanoBio Technol, Taegu 711873, South Korea
[8] Karolinska Inst, Rolf Luft Res Ctr Diabet & Endocrinol, SE-17177 Stockholm, Sweden
[9] Univ Miami, Miller Sch Med, Dept Physiol & Biophys, Miami, FL 33136 USA
[10] Univ Miami, Miller Sch Med, Program Neurosci, Miami, FL 33136 USA
基金
瑞典研究理事会;
关键词
aging; pancreatic islets; glucose metabolism; vasculature; insulin secretion; BETA-CELL FUNCTION; GLUCOSE-HOMEOSTASIS; INSULIN-SECRETION; ENDOTHELIAL-CELLS; BLOOD-FLOW; RAT; INFLAMMATION; EXPRESSION; REVERSES; DETERIORATION;
D O I
10.1073/pnas.1414053111
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
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.
引用
收藏
页码:17612 / 17617
页数:6
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