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)

An increased adherence of leukocytes to the vascular endothelium appears to be a crucial event in the development of atherosclerosis. The role of endothelial cell adhesion molecules is gaining increasingly interest in this context. Several studies show an influence of lipoproteins, especially low-density-lipoproteins on adhesion molecule stimulation. The aim of our study was to analyze the atherogenic potential of postprandially elevated serum triglyceride levels by investigating the impact of postprandial lipoproteins (chylomicrons (CH, isolated 4 h after a standard oral lipid load)) on the expression of E-selectin (endothelial leukocyte adhesion molecule-1, ELAM-1) and VCAM-1 (vascular cell adhesion molecule-1). In addition we used chylomicrons that had been incubated with lipoprotein lipase (50 U/ml) for 3 h (CH-LPL). The endotoxin lipopolysaccharide (LPS) served as positive control for adhesion molecule stimulation. Human umbilical vein endothelial cells (HUVEC) were incubated with the samples for 4 h and expression of E-Selectin and VCAM-1 was determined by ELISA. The expression of E-selectin was induced by LPS (530 +/- 64% compared to the basal activity (= 100%)) and by CH (342 +/- 94%); CH-LPL had no effect on E-Selectin expression. VCAM-1 expression was stimulated by LPS (395 +/- 221%) and similarly by CH-LPL (322 +/- 136%) but considerably stronger by CH (1245 +/- 324). In summary, chylomicrons induced an enhancement of the expression of both adhesion molecules, which closely resembled or even exceeded the endotoxin-induced stimulation. Interestingly, this effect was diminished or even reversed after incubation with LPL.
Exp Clin Endocrinol Diabetes 1997
PMID:Chylomicrons induce E-selectin and VCAM-1 expression in endothelial cells. 928 41

Diabetic retinal neovascularisation is considered to be a consequence of retinal ischaemia caused by capillary occlusion. Capillary occlusion is the result of microvascular thrombi in which erythrocytes, platelets and leucocytes each may play a role. We investigated the role of leucocytes in this process and the subsequent angiogenic response. We studied the serum levels of the soluble leucocyte adhesion molecules soluble E-Selectin, soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1) in the serum of 93 patients with insulin-dependent diabetes (IDDM) and varying degrees of retinopathy and 47 healthy age and sex matched control subjects. We also measured the ability of serum to stimulate retinal capillary endothelial cell migration using an assay of angiogenesis in vitro. Soluble E-Selectin and sVCAM-1 levels were raised in all patients with IDDM (p < 0.001; p < 0.001) particularly those with retinopathy (p < 0.001; p < 0.001). Soluble E-Selectin levels were highest in the patients with severe non-proliferative diabetic retinopathy (p < 0.001) and sVCAM-1 levels were highest in patients with proliferative diabetic retinopathy (p < 0.01). In contrast soluble ICAM-1 levels were the same in patients and control subjects (p > 0.05). Soluble E-Selectin levels in diabetic patients were correlated with the level of glycated haemoglobin (p < 0.05). Retinal endothelial cell migration-inducing (ECMI) activity was increased in patients with IDDM (p < 0.01) in particular in those with retinopathy (p < 0.01). Furthermore, in vitro ECMI activity could be blocked by antibodies to sVCAM-1 and sE-Selectin. These data point to a functional role for leucocyte adhesion in the microvasculopathy of diabetic retinopathy and may have implications for the induction of retinal angiogenesis.
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PMID:Soluble leucocyte adhesion molecules in diabetic retinopathy stimulate retinal capillary endothelial cell migration. 934 97

Metformin effects on insulin resistance and insulin/glucose relationships during an oral glucose tolerance test (OGTT) were investigated in 60 non-diabetic male patients previously treated with coronary artery bypass surgery or angioplasty in an open, 12 week prospective study. During a 4 week run-in period, all patients were treated with diet and lifestyle advice and lovastatin 40 mg daily. Lovastatin treatment was continued in all the patient throughout the study. After randomization, the metformin group got additional treatment with metformin up to 2000 mg/day. Fasting plasma glucose levels and glucose area during OGTT remained unaffected by metformin treatment. Insulin resistance, assessed as the insulin area/glucose area ratio during OGTT decreased by 24% (P = 0.028) in the whole group and by 30% in obese subjects (P = 0.049). Notably, the reduction in body weight by metformin treatment did not correlate with amelioration of insulin resistance or changes in lipid levels. However, changes in insulin resistance correlated with changes in lipid levels. Hence, metformin effects on insulin resistance and body weight appear to be mediated, at least partly, by different mechanisms, while metformin effects on insulin resistance and lipid metabolism are associated in non-diabetic subjects.
Diabetes Res Clin Pract 1998 Jan
PMID:Evidence for dissociation of insulin- and weight-reducing effects of metformin in non-diabetic male patients with coronary heart disease. 959 74

Advanced glycation endproducts (AGEs) possibly play a dominant role in the pathogenesis of macrovascular disease in diabetes. Recent studies could demonstrate that glycated albumin (AGE-BSA) was able to stimulate vascular cell adhesion molecule-1 (VCAM.1) on endothelial cells. The aim of this study was to find out if AGE-BSA was not only able to enhance the expression of vascular cell adhesion molecule-1, but also of intercellular adhesion molecule-1 (ICAM-1) and E-Selectin on human endothelial cells. Stimulation of endothelial cells with AGE-BSA for six hours predominantly increased the expression of VCAM-1, but ICAM-1 and E-Selectin were also upregulated as shown by immunoilluminometric assay (ILMA).
Exp Clin Endocrinol Diabetes 1998
PMID:The influence of advanced glycation endproducts (AGE) on the expression of human endothelial adhesion molecules. 971 Mar 58

The vascular endothelium is the inner lining of all blood vessels and serves as an important autocrine and paracrine organ, that regulates vascular wall functions. Because of its strategic location between the circulating blood and the vascular wall, the endothelium interacts with cellular and neurohumoral mediators, thus controlling vascular contractile state and cellular composition. The vascular endothelium maintains vascular homeostasis by modulating blood vessel tone, by regulating local cellular growth and extracellular matrix deposition and by controlling hemostatic as well as inflammatory responses. One of the best characterized and most important substances released from the endothelium is nitric oxide (NO). NO is a soluble gas which is continuously synthesized from the amino acid L-arginine in endothelial cells by the constitutively expressed nitric oxide synthase. The most important stimuli represent physical factors such as shear stress and pulsatile stretching of the vessel wall as well as circulating and locally released vasoactive substances. The endothelium can be seen as a biosensor, reacting to a large variety of stimuli and therefore maintaining adequate NO release. A large number of risk factors for atherosclerosis including hypercholesterolemia, systemic hypertension, smoking and diabetes have been associated with impaired endothelial NO-mediated vasodilation. "Endothelial dysfunction" is an early marker of atherosclerosis and may be closely related to the disease process. In acute coronary syndromes dysfunctional endothelium may trigger the devastating event of plaque rupture by promoting adhesion of leukocytes, vasoconstriction, activation of platelets and thrombos formation. Atherosclerotic blood vessels are further characterized by activation through zytokines and expression of cellular adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and endothelial-leukocyte adhesion molecule-1 (E-Selectin). After adhesion to the endothelium mononuclear cells migrate to the subendothelial space to take up oxidized LDL, thus transforming into foam cells, a hall mark of early atherosclerotic lesions. A number of conditions including infection with Chlamydia pneumoniae may cause continuous activation of the endothelium and inflammation of the vessel wall. Continuous endothelial dysfunction and activation, caused by risk factors and infection, represent the basis for atherogenesis and acute coronary syndromes.
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PMID:[Endothelial dysfunction--assessment of current status and approaches to therapy]. 1009 15

Hyperlipemia is frequent in liver transplanted patients and has been related with the existence of cholestasis, renal insufficiency, obesity, diabetes, and especially with immunosuppressant treatment. Although there are no studies that show a relationship between post-liver transplant hyperlipemia and the development of cardiovascular disease, there are data that indicate that liver transplanted patients should control their cholesterol levels to reduce the incidence of this disease. When post-transplant hyperlipemia is present, hygienic-dietary measures should be established and treatment should be carried out with the minimum dose of cyclosporine needed to maintain the graft stable. Corticoids should be discontinued as soon as possible. Treatment with some statins (Lovastatin and Pravastatin) has shown to be safe and efficacy in the liver transplanted patients with hypercholesterolemia.
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PMID:[Hyperlipidemia in liver transplanted patients]. 1050 13

The effect of the synthetic statin fluvastatin was investigated on the concentrations of endothelial nitric oxide synthase (eNOS) and of soluble adhesion molecules in human vascular endothelial cell cultures. Fluvastatin was able to increase dose-dependently eNOS concentration. In addition, fluvastatin reduced concentrations of E-Selectin and ICAM-1. These results further support the evidence that statins elicit important effects on the vascular endothelium which may contribute to the reduction of morbidity and mortality of cardiovascular diseases.
Exp Clin Endocrinol Diabetes 2001
PMID:Further evidence for direct vascular actions of statins: effect on endothelial nitric oxide synthase and adhesion molecules. 1140 2

Combined hyperlipidemia (coincident present hypercholesterolemia and hypertriglyceridemia) may contribute to the development of atherosclerosis and coronary artery disease by increasing of cell adhesion molecules (CAMs). Although the cellular expression of CAMs is difficult to assess clinically, soluble forms of CAMs (sCAMs) are present in the circulation and may serve as marker of CAMs. The aim of this study was to determine whether combined hyperlipidemia in overweight adults without clinical evidence of cardiovascular disease, diabetes mellitus or hypertension is associated with increased expression of CAMs. We examined the levels of soluble cell adhesion molecules (sICAM-1, sE-Selectin and sP-Selectin) in blood plasma of overweight adults (n = 36), mean of BMI 27.08 +/- 4.12 kg/m2 with combined hyperlipidemia, with total cholesterol (TC) 7.27 +/- 1.50 mmol/l, LDL cholesterol 4.89 +/- 1.35 mmol/l, HDL cholesterol 1.27 +/- 0.51 mmol/l and triglycerides (TG) 4.08 +/- 2.22 mmol/l before lipid-lowering therapies, and in equal numbers of age, sex and BMI matched controls. Patients with combined hyperlipidemia had significantly higher plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1) (298.13 +/- 41.24 ng/ml versus 241.35 +/- 37.48 ng/ml; P < 0.001), sE-Selectin (63.31 +/- 9.48 ng/ml versus 42.16 +/- 14.18 ng/ml; P < 0.001) and sP-Selectin (161.18 +/- 20.85 ng/ml versus 111.54 +/- 26.12 ng/ml; P < 0.001) compared with overweight, non-hyperlipidemic control subjects. Combined hyperlipidemia in adults with overweight is associated with elevated soluble plasma levels of CAMs. We suppose that levels of CAMs in these patients may be determined as a marker for appreciation of their potential atherosclerotic burden.
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PMID:Increasing plasma levels of soluble cell adhesion molecules (sE-Selectin, sP-Selectin and sICAM-1) in overweight adults with combined hyperlipidemia. 1244 98

Germline mutations in the tumor suppressor gene PTEN (protein phosphatase and tensin homolog located on chromosome ten) predispose to heritable breast cancer. The transcription factor PPARgamma has also been implicated as a tumor suppressor pertinent to a range of neoplasias, including breast cancer. A putative PPARgamma binding site in the PTEN promoter indicates that PPARgamma may regulate PTEN expression. We show here that the PPARgamma agonist Rosiglitazone, along with Lovastatin, induce PTEN in a dose- and time-dependent manner. Lovastatin- or Rosiglitazone-induced PTEN expression was accompanied by a decrease in phosphorylated-AKT and phosphorylated-MAPK and an increase in G1 arrest. We demonstrate that the mechanism of Lovastatin- and Rosiglitazone-associated PTEN expression was a result of an increase in PTEN mRNA, suggesting that this increase was transcriptionally-mediated. Compound-66, an inactive form of Rosiglitazone, which is incapable of activating PPARgamma, was unable to elicit the same response as Rosiglitazone, signifying that the Rosiglitazone response is PPARgamma-mediated. To support this, we show, using reporter assays including dominant-negative constructs of PPARgamma, that both Lovastatin and Rosiglitazone specifically mediate PPARgamma activation. Additionally, we demonstrated that cells lacking PTEN or PPARgamma were unable to induce PTEN mediated cellular events in the presence of Lovastatin or Rosiglitazone. These data are the first to demonstrate that Lovastatin can signal through PPARgamma and directly demonstrate that PPARgamma can upregulate PTEN at the transcriptional level. Since PTEN is constitutively active, our data indicates it may be worthwhile to examine Rosiglitazone and Lovastatin stimulation as mechanisms to increase PTEN expression for therapeutic and preventative strategies including cancer, diabetes mellitus and cardiovascular disease.
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PMID:Increased PTEN expression due to transcriptional activation of PPARgamma by Lovastatin and Rosiglitazone. 1642 25

Endothelial dysfunction plays an important role in the pathogenesis of cardiovascular diseases and diabetes mellitus. However, the causes underlying endothelial dysfunction are not fully understood. Therefore, the aim of the present study was to investigate associations of cardiovascular risk factors with soluble adhesion molecules (sE-Selectin, sICAM-1), soluble thrombomodulin (sTM) and von Willebrand factor (vWF) as markers of endothelial dysfunction. The study population consisted of a subcohort of 2,168 men and women aged 35 to 74 years randomly drawn from three cross-sectional population-based MONICA/KORA Augsburg surveys conducted between 1984 and 1995. In multivariable linear regression analysis, current smoking, high (versus moderate) alcohol consumption, ratio of total cholesterol/HDL-cholesterol (TC/HDL-C) and C-reactive protein (CRP) were significantly associated with elevated levels of sE-selectin and sICAM-1. Increased levels of sE-selectin were also found in subjects with actual hypertension, high body mass index and prevalent diabetes mellitus. In addition, low physical activity and no (versus moderate) alcohol consumption were significantly associated with elevated concentrations of sICAM-1. Levels of sTM were higher in subjects with actual hypertension, no or high amounts of alcohol intake and a high ratio of TC/HDL-C, but were lower in subjects with a history of myocardial infarction. VWF was significantly associated with CRP only. In conclusion, sE-selectin and sICAM-1 are more strongly associated with traditional cardiovascular risk factors than sTM and vWF.
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PMID:Association of cardiovascular risk factors with markers of endothelial dysfunction in middle-aged men and women. Results from the MONICA/KORA Augsburg Study. 1654 72


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