Pancreatic Islet Blood Flow Dynamics in Primates.

Pancreatic Islet Blood Flow Dynamics in Primates.
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灵长类动物中的胰岛血流动力学。

DOI:
10.1016/j.celrep.2017.07.039
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发表时间:
2017-08-08
期刊:
影响因子:
8.8
通讯作者:
Berggren PO
Berggren PO
中科院分区:
生物学1区
文献类型:
--
作者:
Diez JA;Arrojo E Drigo R;Zheng X;Stelmashenko OV;Chua M;Rodriguez-Diaz R;Fukuda M;Köhler M;Leibiger I;Tun SBB;Ali Y;Augustine GJ;Barathi VA;Berggren PO

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胰岛中的血流调节对功能至关重要,但了解甚少。在这里,我们在非人类灵长类动物中建立了一个体内成像平台,其中以单细胞分辨率非侵入性和纵向监测自体移植到眼前房中的胰岛。移植的胰岛血管化和神经支配,并保持原位胰岛在胰腺中的细胞结构。血糖水平升高和/或GLP-1 R激动剂利拉鲁肽未影响移植胰岛中的血流速度。然而,胰岛血流量是动态的,在不同的毛细血管中波动。这与类似括约肌样作用的血管收缩事件相关,最可能受肾上腺素能信号传导调节。这些观察结果表明,灵长类动物胰岛中存在一种机制,将血流转移到代谢需求较高的细胞区域。所描述的成像技术应用于非人灵长类动物胰岛可能有助于更好地了解人类胰岛病理生理学。猴胰岛自体移植到眼前房(ACE)猴ACE胰岛在体内成像,纵向,并在单细胞分辨率猴胰岛血流是动态的,不受葡萄糖/利拉鲁肽治疗方向的血流可以解释胰岛结构-功能关系Diez等。建立一个体内成像平台,在该平台上,对自体移植到眼前房中的猴胰岛进行非侵入性、纵向和单细胞分辨率的监测。与小鼠相比,灵长类动物胰岛中的血流是高度动态的,不受葡萄糖或GLP-1类似物利拉鲁肽的影响。
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. Monkey islets transplanted autologously into the anterior chamber of the eye (ACE) Monkey ACE islets imaged in vivo, longitudinally, and at single-cell resolution Monkey islet blood flow is dynamic and unaffected by glucose/liraglutide treatment Directional blood flow may be explained by islet structure-function relationship Diez et al. establish an in vivo imaging platform where monkey islets transplanted autologously into the anterior chamber of the eye are monitored non-invasively, longitudinally, and at single-cell resolution. In contrast with mice, blood flow in primate islets is highly dynamic and unaffected by glucose or the GLP-1 analog liraglutide.
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期刊: SCIENCE
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