Increased Plasma Levels of Endothelin in Diabetic Patients With Hypertension: An Alternative Viewpoint

Haak, Thomas; Jungmann, E.; Felber, A; Hillmann, U; Usadel, K. H.

doi:10.1093/ajh/5.3.161

Cited by 101 publications

(49 citation statements)

References 9 publications

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“…Earlier studies have shown that circulatory levels of ET-1 are increased in obesity. 10,[20][21][22][23][24] We have recently shown that s.c. adipose tissue, which is the major adipose region, might contribute to the elevated levels of ET-1 in the obese state. 10 This study shows that the expression of ET-1 mRNA is higher in s.c. adipose tissue compared with OM adipose tissue, whereas ETR expression is similar in the two depots .…”

Section: Discussionmentioning

confidence: 99%

Endothelin-1 stimulates human adipocyte lipolysis through the ETA receptor

et al. 2008

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Objective: Levels of the vascular peptide endothelin-1 (ET-1) are significantly elevated in obesity. Adipose tissue-derived ET-1 attenuates insulin-mediated antilipolysis in human visceral adipocytes through the activation of the ET receptor B (ET B R), thereby linking ET-1 to insulin resistance. Whether ET-1 has direct effects on lipolysis in human adipocytes is not known. Research design and subjects: Endothelin-1 receptor (ETR) mRNA expression was determined by quatitative PCR in 130 nonobese and obese subjects. ET-1 mRNA in different adipose tissue regions was also assessed. ETR protein expression was analyzed by western blotting in 37 subjects. The effect of ET-1 on lipolysis was assessed in freshly isolated adipocytes and in vitro differentiated adipocytes from human donors. Results: Freshly isolated human adipocytes incubated with different concentrations of ET-1 showed no acute effect on lipolysis. In contrast, a 24 h incubation in primary cultures of human adipocytes resulted in a significant 50% increase in lipolysis. This effect was concentration dependent and could be mimicked by an agonist of the ET A receptor but not with a selective ET B R agonist. Adipocyte differentiation was not affected by any of the agonists. In subcutaneous (s.c.) adipose tissue from 19 nonobese and 18 obese subjects, the protein expression of ET A R was significantly higher in obese subjects whereas there was no difference in ET B R expression. Interestingly, the differences in protein expression were not observed at the mRNA level as ET A R expression was similar between lean and obese subjects. Conclusion: Long-term but not acute incubation of human adipocytes with ET-1 results in a significant increase in lipolysis. This appears to be mediated through the activation of ET A R, demonstrating a yet another receptor-specific effect of ET-1. In addition, the protein expression of ET A R is increased in s.c. adipose tissue in obesity, possibly through post-transcriptional mechanisms. An increased effect of ET-1 could be a mechanism that contributes to increased basal lipolysis in human obesity.

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Section: Discussionmentioning

confidence: 99%

Endothelin-1 stimulates human adipocyte lipolysis through the ETA receptor

et al. 2008

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“…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.

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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

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“…Plasma ET-1 levels are increased in the diabetic state (Takahashi et al, 1990;Makino & Kamata, 1998;Makino et al, 2001) and the plasma concentration of big endothelin-1, the precursor of ET-1, is elevated in patients with diabetes mellitus (Tsunoda et al, 1991). Thus, although ET-1 may also contribute to the normal maintenance of vascular tone, a pathogenetic role is implied by its overproduction in patients with diabetes (Takahashi et al, 1990;Haak et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Effects of chronic administration of the novel endothelin antagonist J‐104132 on endothelial dysfunction in streptozotocin‐induced diabetic rat

Kanie

Kamata

2002

British J Pharmacology

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1 The biosynthesis of endothelin-1 is increased in the diabetic state. So this peptide may cause diabetic vascular complications. We tested this possibility by chronically administering J-104132, a potent orally active mixed antagonist of endothelin A and B (ET A /ET B ) receptors to streptozotocin (STZ)-induced diabetic rats and focusing on changes in endothelial function. 2 The acetylcholine (ACh)-induced endothelium-dependent relaxation was impaired in diabetic rats and this impairment was signi®cantly attenuated following chronic administration of J-104132 (10 mg kg 71 , p.o., daily for 4 weeks).3 In an in vitro experiment using aortae from diabetic rats, the ACh-induced relaxation was not changed by the presence of J-104132 (3610 79 M). 4 The expression levels of the mRNA for endothelial nitric oxide synthase was comparable among aortae from the three groups (control, diabetic and chronically J-104132-treated diabetic). 5 The amount of superoxide anion was signi®cantly greater in aortae from diabetic rats than in controls. Chronic J-104132 treatment signi®cantly decreased the level of superoxide anion in diabetic rats. 6 The expression of the p22phox mRNA for the NADH/NADPH oxidase subunit was signi®cantly increased in STZ-induced diabetic rats and this increase was completely prevented by chronic administration of J-104132. 7 These results suggest that in STZ-induced diabetic rats, ET-1 may be directly involved in impairing endothelium-dependent relaxation via increased superoxide-anion production.

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Increased Plasma Levels of Endothelin in Diabetic Patients With Hypertension: An Alternative Viewpoint

Cited by 101 publications

References 9 publications

Endothelin-1 stimulates human adipocyte lipolysis through the ETA receptor

Endothelin-1 stimulates human adipocyte lipolysis through the ETA receptor

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

Effects of chronic administration of the novel endothelin antagonist J‐104132 on endothelial dysfunction in streptozotocin‐induced diabetic rat

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