Altered Transendothelial Transport of Hormones as a Contributor to Diabetes

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.

Transendothelial movement of adiponectin is restricted by glucocorticoids

“…Our study was designed investigate the its influence on endothelium permeability and consequently the changes in Ad movement across the endothelium barrier and the underlying mechanism. More recently, a similar proposed mechanism for regulation of Ad action was suggested both by us and others (Rutkowski et al 2014; Yoon et al 2014). To the best of our knowledge, the regulation of this process by glucocorticoids had not been studied before.…”

“…Our vitro model using DEX treated HUVEC and CORT treated rats to integrate the established observations that glucocorticoids can restrict paracellular transport across various endothelia (Keaney and Campbell 2015; Rao, et al 2015; Rochfort and Cummins 2015) with the fact that glucocorticoids, commonly prescribed medications, have numerous side effects, including insulin resistance and diabetes (Beaudry et al 2015). Furthermore, we examined whether the emerging phenomenon that transendothelial movement of Ad may regulate the anti-diabetic effects of this hormone and whether this was regulated by glucocorticoids (Rutkowski et al 2014; Yoon et al 2014). Specifically, our approach involved the use of endothelial cell monolayers and individually perfused intact microvessels to examine whether glucocorticoid altered Ad flux was through reduced microvessel permeability.…”

“…Liver, for example has highly fenestrated endothelium that may permit the passage of HMW Ad, which has potent effects on hepatic metabolism. In contrast, the central effects of HMW Ad may be limited by its transport across the comparatively tighter blood brain barrier (Yoon et al 2014). …”

“…As the primary barrier to the movement of circulating endocrine factors from the bloodstream to the interstitial space, the endothelium plays a critical role in hormone action (Kolka and Bergman 2012; Yoon, et al 2014). Endothelial permeability can significantly impact hormone action by preventing or delaying access of the hormone to target tissues (Kolka and Bergman 2012; Won, et al 2011).…”

“…Endothelial permeability can significantly impact hormone action by preventing or delaying access of the hormone to target tissues (Kolka and Bergman 2012; Won, et al 2011). Transendothelial solute movement can occur via the transcellular pathway where solutes are transported across the endothelium cell membrane or via the paracellular pathway where solutes passively move through the intercellular space between adjacent endothelial cells (Yoon et al 2014) .Previous work has shown that hormone and nutrient concentrations in blood differ from surrounding cells on the tissue side of the blood vessel endothelium (Barrett, et al 2011; Herkner, et al 2003; Yang, et al 1994). Of note, this has been best documented in the case of insulin where concentrations of the hormone are significantly lower in the target tissue than in the circulation (Kolka and Bergman 2012).…”