Increased Plasma Endothelin in NIDDM Patients With Retinopathy

Kawamura, Makiko; Ohgawara, Hisako; Naruse, Mitsuhide; Suzuki, Nobuhiro; Iwasaki, Naoko; Naruse, Kiyoko; Hori, Shingo; Demura, Hiroshi; Omori, Yasue

doi:10.2337/diacare.15.10.1396

Cited by 77 publications

(40 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Several studies have reported increased levels of and attenuated responses to ET-1 in experimental and clinical type 1 and 2 diabetes [10,[27][28][29]. If indeed VEGF is able to maintain the availability of NO in STZ rats, this might result in a decrease in the release of ET-1 [30].…”

Section: Discussionmentioning

confidence: 99%

Chronic treatment with vascular endothelial growth factor preserves agonist-evoked vascular responses in the streptozotocin-induced diabetic rat

et al. 2006

View full text Add to dashboard Cite

Aims/hypothesis: Vascular dysfunction is a hallmark of diabetes mellitus and endothelial dysfunction is considered to be a key early component of vascular dysfunction. Attenuated agonist-evoked responses are considered to be a barometer of endothelial/vascular dysfunction. We sought to determine whether vascular endothelial growth factor (VEGF) could prevent dysfunction from developing in the streptozotocin (STZ)-induced rat model of type 1 diabetes. Materials and methods: One week after induction of diabetes, STZ rats began a 4-week treatment protocol of twice-weekly i.v. injections of 2 μg VEGF or inactivated VEGF. Corresponding non-diabetic rats served as controls. Agonist-evoked vascular responses were recorded 1 day after the last treatment in anaesthetised rats. Results: Acetylcholine (0.1-12.5 μg/kg) evoked increases in superior mesenteric arterial conductance and decreases in mean blood pressure, while methoxamine (12.5-100 μg/kg) and endothelin-1 (100-1,200 pmol/kg) evoked decreases in superior mesenteric arterial conductance and increases in mean blood pressure. These responses to all three agonists were attenuated in STZ rats, and chronic treatment with VEGF improved these responses dramatically. Both the reduction in plasma nitrate and nitrite and the elevation in aortic superoxide associated with STZ diabetes were normalised with VEGF treatment. VEGF also prevented the apparent paradoxical increased endothelial nitric oxide synthase expression seen in untreated STZ rats. Conclusions/interpretation: Chronic treatment with VEGF early in diabetes is able to prevent the attenuated agonistevoked vascular responses in STZ rats and normalise the oxidative environment associated with the disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Chronic treatment with vascular endothelial growth factor preserves agonist-evoked vascular responses in the streptozotocin-induced diabetic rat

et al. 2006

View full text Add to dashboard Cite

show abstract

“…One recent study showed ET-1 concentrations in the vitreous fluid of diabetic patients with proliferative retinopathy are actually decreased compared with non-diabetic control subjects [64]. Moreover, increased plasma ET-1 has been observed in Type II diabetic patients with retinopathy [65,66] but without other end-organ damage related to diabetes [65].…”

Section: In Vivo Haemodynamic Studiesmentioning

confidence: 99%

Endothelin: emerging role in diabetic vascular complications

1999

View full text Add to dashboard Cite

The endothelin (ET) family consists of three 21-amino acid peptides designated ET-1, 2]. The biological actions of the ETs are primarily mediated by two distinct, G-protein-coupled receptor subtypes designated ET A and ET B [2]. Endothelin A receptors have a higher affinity for ET-1 and ET-2 than ET-3 and the ET B receptor binds all three isoforms with equal affinity. Translation of preproET mRNA generates preproET, which is converted to big ET and finally cleaved by ET converting enzyme (ECE) to facilitate production of biologically active peptide. Endothelin-1 released by vascular endothelial cells exerts an autocrine influence by promoting vasodilatation, subsequent to activation of ET B receptors located on endothelial cells. It also exerts a paracrine effect on adjacent vascular smooth muscle cells (VSMC) in evoking vasoconstrictor and mitogenic actions by activation of both ET A and ET B receptors. The primary target of ET-1 is the vasculature where it evokes transient vasodilatation mediated by endothelial ET B receptors, followed by slow-onset and sustained contraction mediated by ET A and ET B receptors located on VSMC. The functional response to ET-1 varies throughout different tissues and vascular beds due to differences in distribution and expression of these two receptor subtypes. Endothelin-1 Diabetologia (1999) AbstractSince the discovery of endothelin-1 as the most potent endothelial-derived vasoconstrictor/mitogenic peptide a decade ago, considerable evidence has implicated this peptide in various cardiovascular disease states, including diabetes mellitus. Plasma and tissue concentrations of endothelin-1 as well as responses to the peptide are changed in various forms of the disease in humans and animals. Endothelin activity is also altered in atherosclerotic and ischaemic disease, nephropathy, retinopathy, erectile dysfunction, and neuropathy, many of the well-known complications of diabetes. Striking new evidence shows that antagonists of the endothelin system might beneficially affect and potentially overcome some of these complications. Despite this, lack of direct proof of causation makes this peptide's role in the disease uncertain. This review examines the current state of thought on the role of endothelin in diabetes and in the complications of the disease as well as the likely roles of altered metabolic variables in modulating endothelin-1 concentrations and its activity. It is concluded that although alterations in endothelin-1 release and action are clearly associated with the diabetic state, further studies using inhibitors of the endothelin system are warranted to determine its precise role in the complications of the disease. [Diabetologia (1999

show abstract

“…Endothelin-1 (ET-1) is not only one of the most potent vasoconstrictors but it also has pro-inflammatory and profibrotic effects, which may contribute to the pathogenesis of nephropathy. In the previous studies, it was demonstrated that serum ET1 level was increased in diabetic patients with microalbuminuria, retinopathy or higher glycosylated hemoglobin (HbA1c) (8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of biochemical and clinical markers of endothelial dysfunction and their correlation with urinary albumin excretion in patients with type 1 diabetes mellitus

Polat

Uğurlu

Aslan

et al. 2016

Arch. Endocrinol. Metab.

View full text Add to dashboard Cite

Objective: Endothelial dysfunction (ED) plays an important role in the pathogenesis of diabetic nephropathy. The purpose of the study was to determine flow mediated endothelial dependent vasodilatation (FMD) measurements and serum soluble (s) endothelin-1 (ET-1), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM-1) levels in patients with type 1 diabetes mellitus (T1DM) with or without increased urinary albumin excretion (UAE) and compare them with the healthy controls. Subjects and methods: Seventy three patients with T1DM were enrolled. Patients were divided into two subgroups according to microalbumin measurements in 24-hr urine collections. The diabetic patients without microalbuminuria (41 patients) were defined as Group I and those with microalbuminuria (32 patients) were defined as group II. A hundred age and sex matched healthy subjects participated as the control group (Group III). Serum sET-1, sICAM-1, sVCAM-1 levels and FMD measurements were determined in all participants. Results: Median FMD measurement was significantly lower in the diabetic groups compared with the control group (6.6, 6.4 and 7.8% in Group I, II and III, respectively) (p < 0.05). FMD was negatively correlated with age (p = 0.042). Median serum sICAM-1 level was higher in the patient groups compared to the control group (p < 0.05). Median serum sVCAM-1 level was higher in the group of patients with increased albuminuria compared to the normoalbuinuric and the control group (p < 0.05). Serum sVCAM-1 level was found to be positively correlated with degree of urinary albumin excretion (p < 0.001). Conclusion: We assume that sVCAM-1 may be used as a predictive marker for risk stratification for nephropathy development and progression. Arch Endocrinol Metab. 2016;60(2):117-24

show abstract

Increased Plasma Endothelin in NIDDM Patients With Retinopathy

Abstract: These results suggest that plasma ET-1 is related to diabetic microvascular disease.

Cited by 77 publications

References 7 publications

Chronic treatment with vascular endothelial growth factor preserves agonist-evoked vascular responses in the streptozotocin-induced diabetic rat

Chronic treatment with vascular endothelial growth factor preserves agonist-evoked vascular responses in the streptozotocin-induced diabetic rat

Endothelin: emerging role in diabetic vascular complications

Evaluation of biochemical and clinical markers of endothelial dysfunction and their correlation with urinary albumin excretion in patients with type 1 diabetes mellitus

Contact Info

Product

Resources

About