Role of endothelin-1 in diabetes mellitus

Chien

Plastic and Reconstructive Surgery

et al. 2016

Section: Discussionsupporting

confidence: 45%

mentioning

confidence: 99%

Endothelin-1 Expression Associated with Lipid Peroxidation and Nuclear Factor-κB Activation in Type 2 Diabetes Mellitus Patients with Angiopathy and Limb Amputation

Chien

Plastic and Reconstructive Surgery

et al. 2016

Experimental Diabetes Research

“…These pathological changes can then induce alterations in the vasculature and is known to support the progression of the disease condition. endothelin-1 (ET-1), a potent vasoconstrictor and mitogen produced by endothelial cells that act on VSMCs, is significantly increased in hyperglycemic/diabetic conditions and plays a critical role in the development of vascular diseases [31, 32]. Additionally, increased activation of protein kinase C (PKC), angiotensin II (ANG-II), increased levels of advanced glycation end products (AGEs), increased plasminogen activity inhibitor-1 (PAI-1), and so forth have been related to endothelial dysfunction in diabetes.…”

Section: Molecular Basis Of Endothelial Dysfunction In Diabetes—cumentioning

confidence: 99%

Endothelial Dysfunction in Diabetes Mellitus: Possible Involvement of Endoplasmic Reticulum Stress?

Basha

Samuel

Triggle

et al. 2012

107

The vascular complications of diabetes mellitus impose a huge burden on the management of this disease. The higher incidence of cardiovascular complications and the unfavorable prognosis among diabetic individuals who develop such complications have been correlated to the hyperglycemia-induced oxidative stress and associated endothelial dysfunction. Although antioxidants may be considered as effective therapeutic agents to relieve oxidative stress and protect the endothelium, recent clinical trials involving these agents have shown limited therapeutic efficacy in this regard. In the recent past experimental evidence suggest that endoplasmic reticulum (ER) stress in the endothelial cells might be an important contributor to diabetes-related vascular complications. The current paper contemplates the possibility of the involvement of ER stress in endothelial dysfunction and diabetes-associated vascular complications.

Journal of Biological Chemistry

“…Recently, several reports have shown that insulin stimulates ET-1 secretion from endothelial cells and also enhances ET-1 binding to its receptors (15). It has also been shown that the plasma ET-1 level is elevated in type II diabetes patients with microvascular complications, suggesting that ET-1 may be involved in diabetes-related complications such as microangiopathy (15,16). Although there is an interest in investigating the role of ET-1 in the development of diabetic complications, very little is known about whether or not the ET system is involved in glucose metabolism.…”

mentioning

confidence: 99%

Endothelin Stimulates Glucose Uptake and GLUT4 Translocation via Activation of Endothelin ETA Receptor in 3T3-L1 Adipocytes

Wu-Wong

Berg

Wang

et al. 1999

Endothelin-1 (ET-1) is a 21-amino acid peptide that binds to G-protein-coupled receptors to evoke biological responses. This report studies the effect of ET-1 on regulating glucose transport in 3T3-L1 adipocytes. ET-1, but not angiotensin II, stimulated glucose uptake in a dose-dependent manner with an EC 50 value of 0.29 nM and a 2.47-fold stimulation at 100 nM. ET-1 stimulated glucose uptake in differentiated 3T3-L1 cells but had no effect in undifferentiated cells, although ET-1 stimulated phosphatidylinositol hydrolysis to a similar degree in both. The 3T3-L1 cells expressed ϳ560,000 sites/ cell of ET A receptor, which was not altered during differentiation. Western blot analysis and immunofluorescence staining show that ET-1 stimulated the translocation of insulin-responsive aminopeptidase and GLUT4 to the plasma membrane. The effect of ET-1 on glucose uptake was blocked by A-216546, an antagonist selective for the ET A receptor. ET-1 treatment did not induce phosphorylation of insulin receptor ␤-subunit, insulin receptor substrate-1, or Akt but stimulated the tyrosyl phosphorylation of a 75-kDa protein. Genistein (100 M), an inhibitor of tyrosine kinases, inhibited ET-1-stimulated glucose uptake. Our results show that ET-1 stimulates GLUT4 translocation and glucose uptake in 3T3-L1 adipocytes via activation of ET A receptor.