在向骨骼肌输送胰岛素的血管系统中起积极作用。

IF 2.4 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Michelle A Vincent, Lucy H Clerk, Stephen Rattigan, Michael G Clark, Eugene J Barrett
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引用次数: 68

摘要

1. 胰岛素被发现80多年来,积累了大量关于胰岛素对人体脂肪、葡萄糖和蛋白质代谢作用的文献。特别是,骨骼肌被广泛研究,因为它作为胰岛素介导的葡萄糖处理的主要部位。肝脏和脂肪组织是胰岛素作用的另外两个被广泛研究的部位。针对胰岛素对肌细胞、脂肪细胞和肝细胞以外的细胞的作用的研究要少得多。2. 在过去的5-10年里,胰岛素对血管细胞的重要作用越来越明显。在这里,我们回顾了胰岛素在肌肉中的作用可能受到其通过血管系统进入间质液(从而进入肌细胞胰岛素受体)的能力的很大程度上的调节。令人惊讶的是,对于首先将胰岛素带到肌肉内毛细血管内皮的血管事件的调控知之甚少,由此推测胰岛素从血管转移到间质空间。最近的研究表明,胰岛素可以增加血流量,也可以影响骨骼肌内血流的分布,因此可能调节其自身向毛细血管内皮的输送。除了胰岛素进入骨骼肌微血管内的血管腔的能力之外,还有胰岛素通过内皮屏障的问题。对于胰岛素在内皮中的实际转运过程,我们所知的就更少了。现有的数据并没有清楚地表明这是一个饱和的、受体介导的过程还是一个被动扩散途径。此外,胰岛素是否以任何方式调节其自身通过内皮细胞的运输或通过淋巴系统的清除是完全未知的。3.本综述的目的是确定知识不足的领域,并强调可能导致更好地理解胰岛素在肌肉中的血管作用及其在该组织中的代谢作用之间的协调关系的假设。即便如此,现在有足够的证据表明,胰岛素在骨骼肌中的血管作用是胰岛素介导的葡萄糖处置的主要调控位点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Active role for the vasculature in the delivery of insulin to skeletal muscle.

1. In the 80+ years since insulin's discovery, an enormous amount of literature has accumulated relating to its actions on body fat, glucose and protein metabolism. In particular, skeletal muscle has been extensively studied because of its major role as a site of insulin-mediated glucose disposal. Liver and adipose tissue are two other extensively studied sites of insulin action. Much less investigation has been directed towards delineating insulin's actions on cells other than myocytes, adipocytes and hepatocytes. 2. Over the past 5-10 years it has become increasingly evident that insulin exerts important actions on vascular cells. Here, we review evidence that insulin's action within muscle may be very much regulated by its ability to transit the vasculature to access the interstitial fluid (and hence the myocyte insulin receptor). Surprisingly little is known regarding the regulation of vascular events that first bring insulin to the capillary endothelium within muscle, whence presumably it transits from the vascular to the interstitial space. Recent studies suggest that insulin can increase blood flow and also influence the distribution of blood flow within skeletal muscle, potentially therefore regulating its own delivery to the capillary endothelium. Beyond insulin's ability to access the vascular lumen within skeletal muscle microvasculature lies the issue of its passing the endothelial barrier. Even less is known about the processes involved in insulin's actual transit across the endothelium. Available data do not clearly indicate whether this is a saturable, receptor-mediated process or a passive-diffusion pathway. Also, whether insulin in any manner regulates its own transit across the endothelium or its clearance via the lymphatic system is entirely unknown. 3. The aim of the present review is to identify areas where knowledge is deficient and highlight hypotheses which may lead to a better understanding of the coordinated relationship between insulin's vascular actions within muscle and its metabolic actions in that tissue. Even so, there is now sufficient evidence to indicate that insulin's vascular action within skeletal muscle is a major regulatory locus for its insulin mediated glucose disposal.

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来源期刊
Clinical and Experimental Pharmacology and Physiology
Clinical and Experimental Pharmacology and Physiology PHARMACOLOGY & PHARMACY-PHYSIOLOGY
自引率
0.00%
发文量
128
期刊介绍: Clinical and Experimental Pharmacology and Physiology is an international journal founded in 1974 by Mike Rand, Austin Doyle, John Coghlan and Paul Korner. Our focus is new frontiers in physiology and pharmacology, emphasizing the translation of basic research to clinical practice. We publish original articles, invited reviews and our exciting, cutting-edge Frontiers-in-Research series’.
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