The Barrier Within: Endothelial Transport of Hormones

Diabetes and Obesity Research Institute, Department of Biomedical Science, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Physiology (Impact Factor: 4.86). 08/2012; 27(4):237-47. DOI: 10.1152/physiol.00012.2012
Source: PubMed


Hormones are involved in a plethora of processes including development and growth, metabolism, mood, and immune responses. These essential functions are dependent on the ability of the hormone to access its target tissue. In the case of endocrine hormones that are transported through the blood, this often means that the endothelium must be crossed. Many studies have shown that the concentrations of hormones and nutrients in blood can be very different from those surrounding the cells on the tissue side of the blood vessel endothelium, suggesting that transport across this barrier can be rate limiting for hormone action. This transport can be regulated by altering the surface area of the blood vessel available for diffusion through to the underlying tissue or by the permeability of the endothelium. Many hormones are known to directly or indirectly affect the endothelial barrier, thus affecting their own distribution to their target tissues. Dysfunction of the endothelial barrier is found in many diseases, particularly those associated with the metabolic syndrome. The interrelatedness of hormones may help to explain why the cluster of diseases in the metabolic syndrome occur together so frequently and suggests that treating the endothelium may ameliorate defects in more than one disease. Here, we review the structure and function of the endothelium, its contribution to the function of hormones, and its involvement in disease.

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    • "Indeed, the efficiency and extent of insulin delivery to the interstitial space can be inhibited physiologically by diet [30]. The mechanism via which insulin crosses the endothelium is at least in part via the paracellular pathway and for more information on this topic readers are referred to recent excellent review articles by Kolka and Bergman [14,31]. "
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    ABSTRACT: The vascular endothelium is a dynamic structure responsible for the separation and regulated movement of biological material between circulation and interstitial fluid. Hormones and nutrients can move across the endothelium either via a transcellular or paracellular route. Transcellular endothelial transport is well understood and broadly acknowledged to play an important role in the normal and abnormal physiology of endothelial function. However, less is known about the role of the paracellular route. Although the concept of endothelial dysfunction in diabetes is now widely accepted, we suggest that alterations in paracellular transport should be studied in greater detail and incorporated into this model. In this review we provide an overview of endothelial paracellular permeability and discuss its potential importance in contributing to the development of diabetes and associated complications. Accordingly, we also contend that if better understood, altered endothelial paracellular permeability could be considered as a potential therapeutic target for diabetes.
    Diabetes & metabolism journal 04/2014; 38(2):92-99. DOI:10.4093/dmj.2014.38.2.92
  • Physiology 08/2012; 27(4):185-6. DOI:10.1152/physiol.00031.2012 · 4.86 Impact Factor
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    ABSTRACT: The vascular endothelium has been identified as an important component in diabetes-associated complications, which include many cardiovascular disorders such as atherosclerosis, hypertension and peripheral neuropathy. Additionally, insulin's actions on the endothelium are now seen as a major factor in the metabolic effects of the hormone by increasing access to insulin sensitive tissues. Endothelial function is impaired in diabetes, obesity, and the metabolic syndrome, which could reduce insulin access to the tissue, and thus reduce insulin sensitivity independently of direct effects at the muscle cell. As such, the endothelium is a valid target for treatment of both the impaired glucose metabolism in diabetes, as well as the vascular based complications of diabetes. Here we review the basics of the endothelium in insulin action, with a focus on the skeletal muscle as insulin's major metabolic organ, and how this is affected by diabetes. We will focus on the most recent developments in the field, including current treatment possibilities.
    Reviews in Endocrine and Metabolic Disorders 01/2013; 14(1). DOI:10.1007/s11154-012-9233-5 · 4.89 Impact Factor
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