Michelle A Vincent, Lucy H Clerk, Stephen Rattigan, Michael G Clark, Eugene J Barrett
{"title":"在向骨骼肌输送胰岛素的血管系统中起积极作用。","authors":"Michelle A Vincent, Lucy H Clerk, Stephen Rattigan, Michael G Clark, Eugene J Barrett","doi":"10.1111/j.1440-1681.2005.04188.x","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"32 4","pages":"302-7"},"PeriodicalIF":2.4000,"publicationDate":"2005-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1440-1681.2005.04188.x","citationCount":"68","resultStr":"{\"title\":\"Active role for the vasculature in the delivery of insulin to skeletal muscle.\",\"authors\":\"Michelle A Vincent, Lucy H Clerk, Stephen Rattigan, Michael G Clark, Eugene J Barrett\",\"doi\":\"10.1111/j.1440-1681.2005.04188.x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":10259,\"journal\":{\"name\":\"Clinical and Experimental Pharmacology and Physiology\",\"volume\":\"32 4\",\"pages\":\"302-7\"},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2005-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1111/j.1440-1681.2005.04188.x\",\"citationCount\":\"68\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical and Experimental Pharmacology and Physiology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1111/j.1440-1681.2005.04188.x\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical and Experimental Pharmacology and Physiology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1111/j.1440-1681.2005.04188.x","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
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.
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’.