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

Endothelial cells were cultured from bovine capillaries and pulmonary arteries, and the effect of insulinlike growth factor (IGF) I and II (multiplication-stimulating activity) and insulin on the synthesis of proteoglycans was determined. IGF I and II stimulated 35SO4 incorporation into proteoglycans in a dose-dependent manner in both microvessel and pulmonary artery endothelial cells with maximum threefold increases. In pulmonary artery cells, the IGFs caused a general stimulation of all classes of glycosaminoglycan-containing proteoglycans. In microvessel endothelial cells, the IGFs appeared to preferentially increase heparan sulfate-containing proteoglycans. Insulin, at concentrations up to 10(-6) M, had no effect on the synthesis of proteoglycans in either microvessel or pulmonary arterial endothelial cells. Thus, the IGFs stimulate the synthesis of proteoglycans in both microvessel and large vessel endothelial cells, a property that is not mimicked by insulin. Because vascular endothelial cells are bathed by IGFs in vivo, such IGF-mediated functions are likely to be significant in both the normal physiology of vascular endothelium and in disease states such as diabetes mellitus.
 ...
PMID:Stimulation of proteoglycans by IGF I and II in microvessel and large vessel endothelial cells. 330 Mar 63

Erythrocytes from patients with diabetes mellitus exhibit increased adherence to cultured human vascular endothelial cells. We investigated the alterations in erythrocyte surface characteristics that may contribute to their abnormal adherence. The organization of phospholipids in the lipid bilayer, as determined by phospholipase A2 treatment and chemical labeling with fluorescamine and trinitrobenzene sulfonic acid (TNBS), is altered in erythrocytes from diabetic patients. Specifically, 12-18% of phosphatidylserine in diabetic erythrocytes (n = 25) is accessible to phospholipase A2 hydrolysis and TNBS labeling, compared to none in normal subjects. These results suggest either a loss in lipid asymmetry or in vivo destabilization of erythrocyte membranes in diabetic patients, causing increased accessibility to phospholipase A2 degradation. The dye merocyanine 540 (MC-540), which is sensitive to the packing of lipids in the bilayer of the membrane, revealed more binding and fluorescence in erythrocytes from diabetic patients than in those from normal subjects. On flow cytometric analysis, 64.5 +/- 17.0% red blood cells (RBCs) in diabetic patients, compared to 35.1 +/- 25.9% RBCs in normal subjects, showed positive MC-540 binding, indicating significant (P less than .001) differences in the packing of lipids in the external leaflet of the bilayer. The results of our study suggest that a loss of lipid asymmetry and/or less ordered packing in the outer leaflet of the diabetic erythrocyte membrane may be responsible for the increased propensity of erythrocytes to adhere to vascular endothelium.
Diabetes 1988 Jan
PMID:Alterations in organization of phospholipids in erythrocytes as factor in adherence to endothelial cells in diabetes mellitus. 333 75

The relationship between diabetic neuropathy on the one hand and microangiopathy and arteriosclerosis on the other was studied by determining plasma 6-keto-prostaglandin F1 alpha (PGF1 alpha) and plasma thromboxane B2 (TXB2) in diabetics with neuropathy. The subjects were 13 patients with insulin independent diabetes mellitus with polyneuropathy (DN+ group), 9 cases which had no neuropathy (DN- group) and 6 control cases. The patients with severe retinopathy, nephropathy and hypertension were excluded. Plasma 6-keto-PGF1 alpha and plasma TXB2 concentration were determined by radioimmunoassay. The motor neuron conduction velocity (M.C.V.) was measured through the tibial nerve in all diabetics. Plasma 6-keto-PGF1 alpha was 116.3 +/- 4.2 pg/ml (mean +/- SE) in the DN+ group and 139.9 +/- 3.0 in the DN- group, each group showing a significant fall over the control with 150.8 +/- 4.5. Plasma 6-keto-PGF1 alpha in the DN+ group showed a significant decrease in comparison with that in the DN- group. As to plasma TXB2, there was no significant difference among the three groups. The M.C.V. fell off significantly in the DN+ group with 52.9 +/- 3.2 m/sec. Furthermore, a significant positive correlation was observed between M.C.V. and plasma 6-keto-PGF1 alpha. The following is the summary of these results. A decrease in plasma 6-keto-PGF1 alpha was observed in diabetics with polyneuropathy. A decrease in the production of prostacyclin (PGI2) due to impairment of vascular endothelium in the nerve tissue was surmised. The decrease in plasma 6-keto-PGF1 alpha presumably stimulates the activity of platelet agglutination and causes an ischemic change in the nerve tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Evaluation of plasma 6-keto-prostaglandin F1 alpha and thromboxane B2 in diabetic neuropathy]. 355 71

BB rats develop spontaneous autoimmune diabetes mellitus characterized morphologically by insulitis, an inflammatory lymphocytic infiltration of the islets of Langerhans. To investigate the role of the vascular endothelium of the pancreas in this destructive process, the authors injected diabetes-prone (DP) and diabetes-resistant (DR) BB/Wor rats as well as other nondiabetic strains of rats with Monastral blue B, a colloidal pigment that identifies leaky microvasculature. They found evidence of a venular defect limited to the pancreas that is specific to the BB rat. Light- and electron-microscopic evidence suggests that this defect is due to a population of trapped (marginating) intravascular monocytes, which may be activated by the colloidal pigment and release vasoactive mediators.
 ...
PMID:A pancreatic venular defect in the BB/Wor rat. 361 25

Use of monoclonal antibodies specific for rat lymphocyte subsets and an anti-insulin marker has allowed us to document the following sequence of events leading to the development of clinical diabetes in this animal model. The first change observed in the pancreas is increased expression of MHC class II molecules on vascular endothelium and this precedes lymphocytic infiltration. Next, T cells of the T helper phenotype infiltrate the pancreas around blood vessels. Many of the infiltrating T cells show class II expression indicating that they are activated. A few cytotoxic and suppressor cells and B lymphocytes are also present and their numbers increase proportionately with rat age. Some macrophages are also seen. Finally, at a late stage class II MHC molecules can be detected in partially destroyed islets on beta cells which are still actively synthesising insulin. We have never observed expression of class II molecules on glucagon or somatostatin secreting cells which are invariably well preserved.
 ...
PMID:Pre-diabetes in the spontaneously diabetic BB/E rat: lymphocyte subpopulations in the pancreatic infiltrate and expression of rat MHC class II molecules in endocrine cells. 389 30

Morphologic and functional abnormalities of vascular endothelium are well recognized in diabetes. In view of our previous finding that high glucose concentrations accelerate death and hamper replication of cultured human endothelial cells, we have investigated in the same model the possibility that exposure to high glucose may result in DNA damage. DNA from human endothelial cells--but not from fibroblasts--exposed to 30 mM glucose for 9-14 d manifested an accelerated rate of unwinding in alkali indicative of an increased number of single strand breaks (P less than 0.001 vs. control). Endothelial cells exposed to high glucose also manifested an increased amount of hydroxy-urea-resistant thymidine incorporation (333 +/- 153 cpm/10(5) cells vs. 88 +/- 42 in control cells, mean +/- SD, P = 0.04), which is indicative of increased DNA repair synthesis. Neither DNA damage nor repair synthesis were increased by medium hypertonicity achieved with 30 mM mannitol. These findings suggest the possibility that, under conditions of high ambient glucose, excess glucose entry in cells that are insulin independent for glucose transport may, directly or indirectly, perturb DNA function. Further, they suggest the possibility that different individual capabilities to repair DNA damage--a process that is under genetic control--may represent a mechanism for different individual susceptibilities to development of diabetic vascular complication.
 ...
PMID:High glucose induces DNA damage in cultured human endothelial cells. 394 57

In diabetes mellitus the vascular endothelium often produces and releases abnormally low amounts of plasminogen activator, leading to an impaired fibrinolytic system, which might be of importance for the development of angiopathy. In this study tests of autonomic neuropathy (AN) were performed on diabetics without autonomic symptoms. It was discovered that diabetics without AN had a significantly lower mean fibrinolytic response to stimulation than nondiabetic controls, whereas this reduction was not found in those with AN. The suggestion that asymptomatic AN might induce a normalization of the impaired fibrinolytic system in diabetes, and thus have a modifying effect on the rate of development of angiopathy, requires further study to be properly evaluated.
Diabetes 1983 May
PMID:Fibrinolytic activity, autonomic neuropathy, and circulation in diabetes mellitus. 660 36

The interaction of insulin with the vascular endothelium was studied using bovine aortic endothelial cells in monolayer cultures. Confluent cell cultures exhibited specific binding of 125I-insulin to high- and low-affinity cell surface receptor sites. Binding was reversible, saturable, and accompanied by internalization and degradation of the bound hormone in a temperature- and time-dependent manner. Pre-exposure of the cultures to insulin resulted in a time-dependent reduction in the availability of cell surface receptors (downregulation). It is concluded that the occurrence of reversible insulin binding and of insulin degradation in endothelial cells supports the concept that the vascular endothelium compartment may regulate the level of insulin in the circulation.
Diabetes 1982 Dec
PMID:Binding, internalization, and degradation of insulin in vascular endothelial cells. 675 20

Von Willebrand factor (VIII: vWf) is a glycoprotein which is essential for normal platelet adhesion to vascular subendothelium, particularly at the high shear rates encountered in small blood vessels. VIII: vWf is distributed in plasma, platelets and subendothelium, though the contributions of each pool to normal hemostasis is unknown. Raised plasma of VIII: vWf have been frequently described in association with diabetes, the highest concentrations being found in patients with retinopathy. In addition, concentrations of VIII: vWf appear to be influenced by the degree of metabolic control of the diabetics, particularly high levels being found during diabetic coma. Plasmatic concentrations of VIII: vWf greater than normal have not been shown to result in increased platelet adhesion or aggregation, so that is seems unlikely that the high levels of plasmatic VIII: vWf contribute directly to the pathogensis of retinopathy. On the other hand, increases in VIII: vWF during episodes of poor metabolic control could be evidence of reversible injury to the vascular endothelium, whereas stable, high concentrations may indicate the presence of microangiopathy.
 ...
PMID:Von Willebrand factor, diabetes mellitus and retinopathy. 679 13

The first phase of the intrinsic coagulation system was studied in twenty-six diabetic outpatients. The parameters tested were kallicrein, prekallicrein, factor XI and factor XII activities. Kallicrein and factor XI showed significantly elevated activities as compared with a normal control group (P less than 0.05 and less than 0.001, respectively). Factor XI and factor XII levels were higher in non-insulin dependent than in insulin dependent diabetics. We found that the kallicrein-prekallicrein system was activated in our diabetic patients and that such activation could probably be secondary to lesions of the vascular endothelium present in long-term diabetics. No correlation was found between glycaemia and activity levels of this system. Our data represent another demonstration of the existence of a hypercoagulable state in diabetes mellitus.
 ...
PMID:Contact phase of blood coagulation in diabetes mellitus. 681 21


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>