Interactions of Endothelin and Insulin: Expanding Parameters of Insulin Resistance

Abstract

Since the discovery of endothelin peptides in the mid-1980s by Yanigasawa and colleagues, accumulating evidence demonstrates that these peptides may function beyond vasoconstriction. Strong epidemiologic associations between insulin resistance and increased endothelin levels or activity have been found, and these associations have prompted studies investigating the interactions of endothelin with insulin. In this review we explore the evidence for such interactions at multiple levels of physiology, ranging from effects on tissue perfusion through modulation of vascular tone to subcellular interactions of endothelin signaling with insulin signaling. The evidence implicating endothelin in insulin resistance and its associated vascular and metabolic abnormalities is reviewed.

Endothelin Receptor Inhibition with Bosentan Delays Onset of Liver Injury in Streptozotocin-Induced Diabetic Condition

“…Together with the findings of experimental trials, which reported that ET receptor blockers decrease fibrosis, it is thought that ET-1 plays an important role in liver fibrosis along with other factors. In particular, the interplay among diabetes, diabetes-related liver diseases, and ET has been documented and claimed to be pathophysiologically relevant in diabetic complications [39][40][41]. In our study, ET-1 mRNA expression in the diabetic liver increased when compared to the healthy group.…”

Glucocorticoid therapy and the risk of equine laminitis

“…Glucocorticoids increase secretion of insulin in a rat model (Sood and Ismail‐Beigi 2010) and hyperinsulinaemia has, besides the reduction in endothelial NO production, also been associated with elevated concentrations of the potent vasoconstrictor ET‐1 (Juan et al . 1999; Strawbridge et al . 2006; Tousoulis et al .…”

“…The regulation of digital blood flow is, however, not simply under the control of one mediator but is due to a complex interplay between vasoconstrictors such as endothelin (ET) and vasodilators such as NO (Cardillo et al 1999;Miller et al 2002). Glucocorticoids increase secretion of insulin in a rat model (Sood and Ismail-Beigi 2010) and hyperinsulinaemia has, besides the reduction in endothelial NO production, also been associated with elevated concentrations of the potent vasoconstrictor ET-1 (Juan et al 1999;Strawbridge et al 2006;Tousoulis et al 2008). In addition, hyperinsulinaemia in both a rat model as well as in diabetic patients can lead to excess arteriovenous blood shunting as a consequence of altered vasomotor tone (Stevens et al 1991;Kihara et al 1994).…”

Chapter 20 Retinal Insulin Receptor Signaling In Hyperosmotic Stress

“…. Tyrosine phosphorylated IRS-1 and Cbl harbor signaling proteins involved in activation of PI3K/Akt survival pathway and F-actin polymerization, respectively (Strawbridge et al, 2006). Previous studies have shown that type 2 diabetes, obesity, metabolic syndrome X and age related insulin resistance were characterized by elevated levels of vasoactive peptide endothelin-1 (ET-1) (Sayama et al, 1999;Ferri et al, 1995;Ferri et al, 1997).…”

“…. ET-1 peptide induced defects in lipid membrane, impaired PI3K signaling, reduced tyrosine phosphorylation of Cbl and F-actin polymerization as well as GLUT4 trafficking when added to insulin- or sorbitol-incubation conditions; thus, ET-1 challenges and overwrites protective role of Cbl (Strawbridge et al, 2006). Taken together, previous and our current findings suggest that under normal conditions Cbl negatively regulates p85 whereby it potentially minimizes the available PI3K pool utilized for basal signaling by RTK and non-RTK.…”