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)

We examined the ability of fibronectin, an extracellular glycoprotein that interacts with cell surfaces and matrix components, to bind to glomerular basement membrane and the effect of diabetes on this binding. 125I-labeled fibronectin binding to rat glomerular basement membrane (GBM) was dose dependent, related to time and amount of basement membrane, and inhibited by unlabeled fibronectin but not by unrelated proteins. Binding was reduced approximately 60% when GBM was pretreated with collagenase and approximately 24% when pretreated with chondroitinase plus heparinase. Treatment with NaCl had little effect on binding, whereas reduction with beta-mercaptoethanol removed approximately 25% of the bound 125I-fibronectin. Binding to samples prepared from rats with streptozocin-induced diabetes was significantly increased compared with that observed with control preparations at all concentrations of fibronectin and of basement membrane tested. The findings provide direct evidence that fibronectin binds to GBM and that this binding, which represents a biologic function of the protein, is enhanced in diabetes.
Diabetes 1987 Jun
PMID:Fibronectin binding to glomerular basement membrane is altered in diabetes. 356 74

A direct correlation exists between collagenization of Disse's space and the presence of diabetic microangiopathy in type I diabetes. To confirm and extend this finding, we studied four liver biopsy samples from two patients with type I diabetes (one with retinopathy) and two patients with type II diabetes (no retinopathy). All had normal or subnormal results on liver function tests and normal liver architecture. Levels of collagen types I, III, and IV, laminin, and fibronectin, as determined by immunocytochemical techniques, appeared increased in all patients. Liver biopsy samples were perfusion fixed for electron microscopy of sinusoids and sinusoidal cells. Numerous and thick collagen bundles could be seen in Disse's space, as could the increase of basement membrane-like material underlying the endothelial cells, perisinusoidal cells, and sinusoidal membrane of hepatocytes. Perisinusoidal cells were active and had abundant rough endoplasmic reticula and thick processes. This preliminary study indicates that collagenization of Disse's space is not specific to a certain type of diabetes. The increase of basement membrane-like material raises the question of whether liver sinusoids are truly different from other capillaries as far as diabetic microangiopathy is concerned.
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PMID:Perisinusoidal fibrosis and basement membrane-like material in the livers of diabetic patients. 361 Jan 29

Plasma fibronectin (FN) is a high-molecular weight glycoprotein produced by endothelial cells, fibroblasts, and other mesenchymal cells. Plasma FN levels were measured in non-insulin-dependent diabetics (NIDDM) (n = 42) and compared with age-matched control subjects (n = 20). Plasma FN levels were significantly higher in the NIDDM patients (44.2 +/- 2.2 mg/dl, mean +/- SE) than in the control subjects (31.2 +/- 2.2 mg/dl). In addition, the rate of platelet aggregation was studied in 23 of the 42 NIDDM patients. Interestingly, the plasma FN levels were significantly elevated, particularly in diabetic patients with enhanced platelet aggregation. It is suggested that elevated plasma FN may be closely related to the abnormality of platelet function in diabetics, which leads to diabetic vascular lesions.
Diabetes Res Clin Pract 1986 May
PMID:Plasma fibronectin and platelet aggregation in diabetes mellitus. 372 May 1

To establish the relation between plasma fibronectin (PF) and vascular complications of diabetes mellitus, we studied 163 normotensive diabetic outpatients, of whom 53 were treated with insulin (15 type I, 38 type II) and 110 with sulfonylureas, and compared them to 34 control subjects. Diabetic patients were divided, according to their therapy, into four groups: with retinopathy (classified as background or proliferative) detected by fluorescein angiography (m), with macroangiopathy, assessed by clinical criteria (M), with both vessel complications (mM) and without vascular disease (N). PF was not related to glycosylated hemoglobin (HbA1) in each treatment group (r = 0.26; P = 0.051 in the insulin treated patients and r = 0.09; P = 0.356 in the group on oral drugs). PF levels were similar in M groups, either on insulin or sulfonylureas and in controls. Both m and mM subsets of patients were, conversely, characterized by significantly raised mean PF concentrations when compared to N subjects or controls, but proliferative retinopathy was not associated with a significant PF increase compared to background retinopathy. The differences of PF levels among m, mM and N groups remained significant after processing the data by means of stepwise discriminant analysis with age, duration of diabetes, body weight and HbA1 entering the model as covariates. We conclude that diabetic macroangiopathy is not associated with modifications of mean PF levels, which, on the contrary, appear increased only in diabetic patients with retinopathy, regardless of their therapy.
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PMID:Plasma fibronectin in diabetic retinopathy and macroangiopathy. 377 Feb 74

Diabetes mellitus induces alterations in the metabolism of the macromolecules present in the intercellular matrices and particularly in the basement membranes. These contribute to the morphological changes characteristic of the disease : basement membrane thickening, skin thickening and induration. Accumulation of overglycosylated collagens and diminution of sulfated proteoglycan concentrations are the most generally reported biochemical modifications in human or animal diabetic states. More limited data are available concerning elastin, fibronectin and laminin in diabetes.
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PMID:Connective tissue in diabetes mellitus: biochemical alterations of the intercellular matrix with special reference to proteoglycans, collagens and basement membranes. 388 3

The diagnosis of light chain deposition nephropathy is based on the immunohistochemical demonstration of monoclonal light chain deposits within connective tissue matrix and on the presence at the ultrastructural level of electron-dense granular deposits along glomerular and tubular basement membranes. A nodular glomerulopathy characterized by amorphous periodic acid-Schiff-positive and argyrophilic widened mesangium and nodules is described in three patients with light chain deposition nephropathy. Light microscopic examination did not allow discrimination between the glomerular changes found in these specimens and the nodular glomerulosclerosis described in four patients with well-documented diabetes mellitus. Electron microscopic examination revealed microtubular fibrils 10 to 12 nm thick in mesangial areas in both groups. Such microfibrils could be glycoproteins. Immunofluorescence localization of matrix proteins, by staining with affinity-purified antibodies to types I, III, IV, and V (A, B) collagens, fibronectin, laminin, and heparan sulfate-containing proteoglycans, showed similar distributions in the two conditions. The mechanism of this abnormal accumulation of mesangial and glomerular basement membrane matrix proteins in two different conditions remains unknown.
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PMID:Glomerular matrix proteins in nodular glomerulosclerosis in association with light chain deposition disease and diabetes mellitus. 392 52

This study reports the nonenzymatic glycation of plasma fibronectin in vivo in diabetic dogs and also in vitro by incubation of human plasma fibronectin with excess glucose. Although no difference is observed in the total plasma fibronectin level, the nonenzymatic glycation of fibronectin is increased 2.3-fold in inbred male beagle dogs made diabetic with alloxan in comparison with age-matched controls. The extent of non-enzymatic glycation of fibronectin is shown to be proportional to blood glucose levels. HPLC reverse-phase analysis of the hydrolyzed amino acids and glyco-amino acids from plasma fibronectin samples of normal and diabetic dogs show that nonenzymatic glycation occurs only on lysine residues. When purified human plasma fibronectin was incubated in vitro with 500 mM glucose, the extent of nonenzymatic glycation of fibronectin was observed to increase proportionately with time. Ligand binding assays conducted in solution with varying concentrations of 3H-heparin in the presence of a constant amount of normal or nonenzymatically glycated human plasma fibronectin gave virtually identical binding curves. However, the binding of 3H-heparin to normal fibronectin could be increased fourfold by the concomitant addition of normal gelatin (denatured calfskin collagen). If in vitro glycated fibronectin and/or in vitro glycated gelatin are added under this latter condition with 3H-heparin, there is a tremendous decrease in the expected heparin binding seen with normal levels of nonenzymatic glycation. Other experiments were performed to quantitate the binding of 3H-labeled fibronectin to gelatin-coated nitrocellulose filters. Nonenzymatic glycation of fibronectin in vitro resulted in markedly decreased binding of 3H-fibronectin to collagen.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1985 May
PMID:Nonenzymatic glycation of fibronectin and alterations in the molecular association of cell matrix and basement membrane components in diabetes mellitus. 398 74

Plasma concentration of fibronectin, a recently characterized high molecular mass glycoprotein, was determined in patients with peripheral vascular disease. The plasma fibronectin concentration was lower in patients with peripheral obstructive arterial disease as well as in patients with venous disease, than in corresponding healthy controls. Patients with venous disease had significantly lower levels of plasma fibronectin than patients with peripheral obstructive arterial disease. The patients with peripheral arterial disease were divided into two groups, one having diabetes and another not having diabetes respectively. Between these two groups there was no significant difference in plasma fibronectin concentration.
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PMID:Level of plasma fibronectin in patients with peripheral vascular disease. 405 8

The adhesion of blood cells to endothelium can be studied in vitro using human endothelial cells in culture. This experimental model and radiometric techniques provide us with a simple system to quantify the adhesion of blood cells to endothelium. Normal human granulocytes isolated by density gradient adhere to normal endothelial cells in a proportion of 25%. Human promyelocytic cells (HL 60) induced by retinoic acid into mature cells adhere as well as normal granulocytes while the noninduced adhere poorly to endothelium. A small percentage of normal red cells attach to endothelial cells while red cells from patients with sickle cell anemia or diabetes mellitus have a significantly increased adhesion to endothelial cells (P greater than 0.001). This adhesion is statistically correlated with the extent and severity of vascular complications in diabetes mellitus (P less than 0.05). The addition of fibrinogen significantly increased (P less than 0.01) the adhesion of normal red cells, red cells from patients with sickle cell anemia or diabetes mellitus while gamma-globulins did not modify adhesion. Fibronectin potentiated the adhesion of normal red cells.
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PMID:Factors involved in cell adhesion to vascular endothelium. 619 16

Distribution of the fibronectin (FN) present in the forearm skin was studied in 23 controls and 34 insulin dependent diabetics. All the subjects were lean males under 50 years. After biopsy FN was studied by an indirect immunofluorescence technic. A semi-quantitative evaluation was attempted by giving a score to the fluorescent intensity read at the three following sites: vascular basement membranes, papillary dermis, and the dermo-epidermal basement membranes. We found an increased amount of FN-immunofluorescence in diabetic skins. This increase was seen not only in vascular basement membranes but also at the two other sites. No correlation was found between apparent FN levels and the duration or equilibration of diabetes. These results are consistent with other findings of the literature concerning the involvement of the intercellular matrix in diabetes.
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PMID:Distribution of fibronectin in diabetic skin. 634 66


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