Pancreatic Islet Blood Flow Dynamics in Primates

被引:29
作者
Diez, Juan A. [1 ,2 ]
Arrojo e Drigo, Rafael [1 ,2 ,3 ]
Zheng, Xiaofeng [1 ,2 ]
Stelmashenko, Olga V. [1 ,2 ]
Chua, Minni [1 ]
Rodriguez-Diaz, Rayner [4 ]
Fukuda, Masahiro [1 ,5 ]
Kohler, Martin [6 ]
Leibiger, Ingo [6 ]
Tun, Sai Bo Bo [2 ]
Ali, Yusuf [1 ]
Augustine, George J. [1 ,7 ]
Barathi, Veluchamy A. [2 ,8 ,9 ]
Berggren, Per-Olof [1 ,2 ,6 ,10 ,11 ]
机构
[1] Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore 637553, Singapore
[2] Singapore Gen Hosp, SERI, Translat Preclin Model Platform, Singapore 168751, Singapore
[3] Nanyang Technol Univ, NISB, Singapore 636921, Singapore
[4] Univ Miami, Miller Sch Med, Dept Med, Div Endocrinol Diabet & Metab, Miami, FL 33136 USA
[5] Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Dept Mol Therapy, Kodaira, Tokyo 1878551, Japan
[6] Karolinska Univ Hosp L1, Karolinska Inst, Rolf Luft Res Ctr Diabet & Endocrinol, S-17176 Stockholm, Sweden
[7] Inst Mol & Cell Biol, A STAR, Singapore 138673, Singapore
[8] DUKE NUS Grad Med Sch, Ophthalmol & Visual Sci Acad Clin Program, Singapore 169856, Singapore
[9] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore
[10] Imperial Coll London, London SW7 2AZ, England
[11] Univ Miami, Miller Sch Med, Diabetes Res Inst, Miami, FL 33136 USA
来源
CELL REPORTS | 2017年 / 20卷 / 06期
基金
英国医学研究理事会; 瑞典研究理事会;
关键词
BETA-CELL FUNCTION; NONHUMAN PRIMATE; INNERVATION; GLUCOSE; ARCHITECTURE; SECRETION; VESSELS; SIGNAL; MODEL;
D O I
10.1016/j.celrep.2017.07.039
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Blood flow regulation in pancreatic islets is critical for function but poorly understood. Here, we establish an in vivo imaging platform in a non-human primate where islets transplanted autologously into the anterior chamber of the eye are monitored non-invasively and longitudinally at single-cell resolution. Engrafted islets were vascularized and innervated and maintained the cytoarchitecture of in situ islets in the pancreas. Blood flow velocity in the engrafted islets was not affected by increasing blood glucose levels and/or the GLP-1R agonist liraglutide. However, islet blood flow was dynamic in nature and fluctuated in various capillaries. This was associated with vasoconstriction events resembling a sphincter-like action, most likely regulated by adrenergic signaling. These observations suggest a mechanism in primate islets that diverts blood flow to cell regions with higher metabolic demand. The described imaging technology applied in non-human primate islets may contribute to a better understanding of human islet pathophysiology.
引用
收藏
页码:1490 / 1501
页数:12
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