Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The levels of endothelins 1 and 2 (ET-1 and ET-2) have been examined in 415 follicular fluids of 57 women participating in the IVF-ET programme in the University Women's Hospital, Marburg, in relation to the morphological appearance ("maturity") and fertilizability of harvested oocytes as well as to the levels of inhibin, FSH, IGF-1, estradiol and progesterone. Follicular aspiration was done transvaginally in all patients after down regulation with nafareline and ovarian stimulation using urofollitropin and menotropin. Ovulation was induced by hCG. ETs were measured by RIA using commercial kits supplied by Peninsula Laboratories, Belmont, CA. For FF samples, ET-1 and ET-2 RIAs were revalidated. Immunoreactive ET-1 was detectable in all follicular samples, the average level being 18.5 +/- 11.8 pg/ml, ET-2 was present only in 67.5% of the samples, the average level being 13.6 +/- 16.3 pg/ml. There was no significant difference in the average levels of ET-1 in the fluids of small, medium and large follicles. However, there was a significantly higher level of ET-2 in the fluids of medium compared to large follicles and there was a negative correlation of the ET-2 levels to the volume of the follicle (p < 0.01) which suggests that ET-2 could play a role during the maturation of the ovarian follicles. Unlike ET-1, the mean concentrations of ET-2 were significantly higher in the fluids with oocytes which could be fertilized and cleaved than in those with oocytes which did not fertilize or cleave, thus indicating a role for ET-2 in the process of oocyte maturation. No correlations of ET levels were found with the levels of inhibin, FSH, estradiol and progesterone. However, ET-2 levels significantly correlated with the levels of IGF-1 (p < 0.001) indicating a possible synergistic effect of endothelins and IGF-system. In conclusion, this study is further evidence for a physiological role of the ETs in the human ovary.
Exp Clin Endocrinol Diabetes 1996
PMID:Human follicular fluid levels of endothelins in relation to oocyte maturity status. 875 May 75

The aims of this study were to assess whether high-dose treatment with an endothelin 1 (ET1) ETA antagonist could correct deficits in peripheral nerve conduction and blood flow in streptozotocin-diabetic rats and to examine interactions between ET1 and the renin-angiotensin system using low-dose single and combined treatments with ETA and AT1 antagonists. After B wk of diabetes, sciatic motor nerve conduction velocity (NCV) was approximately 20% reduced. High-dose ETA antagonist treatment for 2 wk corrected NCV to the extent of 84%. A approximately 48% diabetic deficit in nutritive endoneurial blood flow was also 88% corrected by the ETA antagonist. Combined treatment with low-doses of ETA and AT1 antagonists, selected to give approximately 20% amelioration of diabetic NCV deficits on their own, resulted in 66% correction. This was greater than expected for a simple additive effect between the antagonists, demonstrating a synergistic interaction. From NCV dose-response curves, the combined treatment effect was equivalent to a 4.2- to 8.9-fold dose increase for the individual antagonists. In parallel, joint treatment markedly improved sciatic nutritive endoneurial perfusion. Thus, the data strongly implicate ET1, acting via ETA receptors in the etiology of neurovascular dysfunction in experimental diabetic neuropathy. Furthermore, they demonstrate synergistic interactions between ET1 and renin-angiotensin systems that, if present in neuropathic patients, could potentially be used to obtain a therapeutic advantage.
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PMID:Effects of a nonpeptide endothelin-1 ETA antagonist on neurovascular function in diabetic rats: interaction with the renin-angiotensin system. 881 10

Acute hyperinsulinemia does not increase circulating ET-1 levels in subjects with normal and deranged glucose metabolism.
Diabetes Res Clin Pract 1996 May
PMID:Lack of acute insulin effect on plasma endothelin-1 levels in humans. 885 8

We investigated whether nitric oxide (NO) contributes to glomerular hyperfiltration in experimental diabetes. Thirty-five adult male Munich-Wistar streptozocin-diabetic rats and 39 nondiabetic controls were distributed among 4 groups: C, normal control; C + L-NAME, controls receiving the NO inhibitor N omega-nitro-L-arginine methyl ester (L-NAME), 40 mg/dl in drinking water; DM, diabetic rats; DM + L-NAME, diabetic rats receiving L-NAME, 15 mg/dl in drinking water. After 1 month of treatment, the DM + L-NAME group exhibited renal vasoconstriction and lacked hyperfiltration. Acute administration of L-NAME, 2.5 mg/kg, depressed the glomerular filtration rate and promoted renal vasoconstriction to a much greater extent in the DM than in the C group. Acute administration of endothelin 1 (600 ng/kg, bolus) or angiotensin II (25 micrograms/kg/min, continuous infusion) exerted similar hemodynamic effects in the C and DM groups, suggesting that the enhanced response of DM to L-NAME reflected specific sensitivity to NO inhibition. Urinary excretion of nitrites and nitrates was fourfold higher in DM compared to C. These results support the notion that augmented NO production may contribute to renal hyperfiltration and hyperperfusion in diabetes.
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PMID:Renal effects of acute and chronic nitric oxide inhibition in experimental diabetes. 888 32

As there is increasing evidence that diabetes induces changes in the plasma levels of endothelins (ETs) and in the properties of ET receptors in peripheral tissues, and as there are reports indicating the presence of significant amounts of ET receptors in mammalian vasa deferentia, we studied possible alterations in ET receptor characteristics in the vasa deferentia of the following groups of rats: 8 weeks diabetic (D8), 8 weeks age-matched control (C8), 16 weeks diabetic (D16), 16 weeks diabetic-insulin-treated (started 8 weeks after the onset of diabetes) (DI16), and 16 weeks age-matched control (C16). Diabetes was induced by the i.v. injection of 65 mg/kg streptozotocin (STZ). Diabetic rats had hyperglycemia, hypoinsulinemia, glucosuria, polydipsia, and polyuria and had smaller vasa deferentia than control and diabetic-insulin-treated animals. Receptor binding experiments with [125I]ET-1 demonstrated that the densities of ET receptors in vasa deferentia from D8, C8, D16, DI16, and C16 animals were 377 +/- 11, 255 +/- 24, 315 +/- 18, 210 +/- 12, and 214 +/- 7 fmol/mg of protein, respectively. [125I]ET-1 binding to the ET receptors was inhibited by ET-1 (non-selective), BQ 610 (ETA selective), ET-3 (ETC selective), and IRL 1620 (ETB selective) with the following rank order of Ki values: ET-1 < BQ 610 < ET-3 < < IRL 1620. The pharmacological profile of the ET receptors was similar in all groups and was consistent with the predominance of the ETA receptor subtype in the rat vasa deferentia. Our data indicate that experimental diabetes up-regulates the density of ET receptors in the rat vasa deferentia and that the receptor up-regulation is reversed by insulin treatment.
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PMID:Characterization of endothelin receptors in streptozotocin-induced diabetic rat vas deferens. 893 75

Endothelins (ETs) are a family of vasoactive peptides implicated in several disorders of the microvasculature. In the present study, the distribution of immunoreactive ET-1 and ET-3 was investigated in eyes from 8 month spontaneously diabetic BB/W rats and in age matched control animals. Both peptides showed similar immunoreactivity. In non-diabetic animals, corneal epithelium and endothelium, ciliary epithelium, lens epithelium, iris and the microvasculature of the sclera and choroid showed positive immunoreactivity. In the retina, photoreceptor inner segments showed positivity. In the inner nuclear layer, cells of both neuronal and glial origins showed positive immunoreactivity. Both the nuclei and the cytoplasm of the ganglion cells were positively stained. Retinal pigment epithelium showed patchy but consistent immunoreactivity. Capillary endothelial cells showed inconsistent positive staining. The pericytes were uniformly negative. In diabetic animals although overall intensity was increased, retinal pigment epithelium and ciliary epithelium showed no immunoreactivity. The corneal epithelium showed increased but patchy immunoreactivity. The altered intensity and distribution of ETs in diabetes suggest that ETs may be of importance in the pathogenesis of chronic occular complications in the diabetic BB/W rat.
Diabetes Res Clin Pract 1997 Aug
PMID:Endothelin-1 and endothelin-3-like immunoreactivity in the eyes of diabetic and non-diabetic BB/W rats. 927 81

We evaluated venous plasma ET-1 concentrations in 18 never-treated obese men (body mass index 31.0 +/- 0.5 kg/m2; age 45.4 +/- 4.3 years) showing the whole features of the above syndrome and 12 control men (age 44.1 +/- 3.6 years). Circulating ET-1 levels were significantly higher in patients than in controls (p < 0.05), and were directly correlated with fasting insulin levels (r = 0.564, p = 0.015) and erythrocyte Na+/Li+ counter-transport activity (r = 0.504, p = 0.033). In conclusion, venous plasma ET-1 levels are elevated in obese men manifesting the whole features of the metabolic syndrome. Due to the biological properties of ET-1, our findings suggest the peptide as a further component of the cluster of cardiovascular risk factors which characterizes this syndrome.
Exp Clin Endocrinol Diabetes 1997
PMID:Circulating endothelin-1 levels in obese patients with the metabolic syndrome. 928 42

Increased levels of endothelin (ET-1), a potent endothelium-derived vasoconstrictive peptide, have been found in plasma from non-insulin dependent diabetic (NIDDM) patients, suggesting that ET-1 might represent a new marker of diabetes-related vascular damage. To elucidate this topic, circulating ET-1 levels were evaluated in 16 NIDDM patients in good metabolic control without either cardiovascular risk factors (obesity, hypertension, smoking, hyperdislipidaemia, etc.) or diabetes-related damage of other districts and in 12 healthy subjects. Retinopathy was assessed by ophthalmological evaluation and its severity determined by Klein criteria. Resulting data showed higher levels of plasma ET-1 in NIDDM patients than in control subjects (0.80 +/- 0.13 vs 0.60 +/- 0.12 pg/mL, p < 0.001). Plasma ET-1 levels were directly correlated with retinopathy degrees in NIDDM patients affected by retinopathy (n = 10; r = 0.368; p = 0.02), and were significantly higher in these latter (n = 10) than in those without retinopathy (n = 6) (0.89 +/- 0.13 vs 0.71 +/- 0.19 pg/mL, p < 0.05). The increased levels of ET-1 could contribute to retinopathy development or, more probably, represent a marker of this diabetes-related complication.
Exp Clin Endocrinol Diabetes 1997
PMID:Increased levels of plasma endothelin-1 in non-insulin dependent diabetic patients with retinopathy but without other diabetes-related organ damage. 928 43

We investigated the binding characteristics of endothelin (ET) receptors in the ureters of rats with experimentally induced diabetes and diuresis. Receptor binding experiments demonstrated an upregulation in the expression of [125I]ET-1 binding sites in the diabetic rat ureter but not in the diuretic rat ureter. ET-1, ET-3, IRL 1620, and BQ 610 inhibited [125I]ET-binding to the rat ureter consistent with the predominance of ETA receptors in these tissues. The subtype specificity of ET receptors in ureteral tissues was confirmed with inhibition data obtained from cloned human ETA and ETB receptors.
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PMID:Experimental diabetes upregulates the expression of uretereral endothelin receptors. 935 71

Plasma ET-1 was measured around the clock on different calendar dates in healthy subjects and in subjects with diabetes and/or with high blood pressure and/or a history of vascular complications (HVDR). A transverse approach, with each subject contributing a single 24-h mean, assessed any about-weekly or half-weekly variation in ET-1. A circasemiseptan component resolved by single cosinor for nondiabetic (but not for diabetic) HVDR subjects (p = 0.010) differs in its timing of overall high values (p < 0.050) from that found in healthy subjects (p = 0.006). The results are aligned with circasemiseptan patterns in other circulatory variables and morbidity/mortality statistics.
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PMID:About-half-weekly (circasemiseptan) component of the endothelin-1 (ET-1) chronome and vascular disease risk. 939 67


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