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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In our previous studies in experimental diabetic rats, we have observed close similarities of ultrastructure and accumulation of IgG and IgM between the mesangial expansion and arteriolar hyalinosis of the glomerulus, and have presumed that both diabetic lesions are essentially of similar nature. In the present study, we carried out a further study on the constituents of both these lesions, using the PA-TCH-SP-PD technique for neutral carbohydrates, sialic acid and glycoproteins and the IgG-gold-silver technique for type IV collagen and fibronectin. The above staining and immunolabelings proved to be comparable in both lesions of diabetic glomerulopathies. This argues for the hypothesis of the identity of the two lesions.
Diabetes Res Clin Pract 1992 Dec
PMID:Similarity of the constituents between glomerular arteriolar and mesangial lesions in experimental diabetes. 128 17

Renal disease is one of the most common and severe complications of diabetes mellitus. The hallmark of the disease, glomerulosclerosis, is characterized by an accumulation of extracellular matrix in the mesangial areas, leading to progressive obliteration of the vascular spaces. The role of the metabolic derangements of diabetes mellitus in the development of these lesions is incompletely understood. One of the consequences of hyperglycemia is the formation of advanced glycosylation end products (AGEs), which result from a series of rearrangements secondary to nonenzymatic reaction of glucose with proteins. Specific receptors for proteins modified by AGEs, present in several cell types, were recently described in human and rat mesangial cells. Furthermore, exposure of mesangial cells to AGEs was followed by an increase in fibronectin production. In the present study we show evidence that mouse mesangial cells exhibit an increase in collagen type IV mRNA and peptide synthesis after exposure to AGEs. Antibodies to AGE receptors prevent this increase, indicating that the response is AGE-receptor-mediated. In addition, anti-platelet-derived growth factor abrogates the AGE response, suggesting that platelet-derived growth factor acts as an intermediate factor. Transcription assay reveals that the elevated mRNA levels are due to an increase in the transcription rate, rather than to an increase in the stability of the message. Finally, the mRNAs coding for laminin and heparan sulfate proteoglycan are also increased after exposure to AGE, whereas glyceraldehyde 3-phosphate dehydrogenase mRNA levels remain constant. The increase in extracellular matrix mRNAs seen in the current study suggests that AGE formation in vivo may be one of the metabolic events leading to the development of diabetic glomerulosclerosis.
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PMID:Receptor-specific increase in extracellular matrix production in mouse mesangial cells by advanced glycosylation end products is mediated via platelet-derived growth factor. 131 71

Fibronectin is a plasma glycoprotein which is involved in coagulation, platelet function, tissue repair and the vascular endothelial basement membrane. To ascertain the influence of pregnancy on plasma concentrations of fibronectin, we qualified plasma concentrations of fibronectin in normal pregnant women during the first, second and third trimester; at the time of delivery; and on the third day post partum, using a radial immunodiffusion plate procedure. The concentrations of fibronectin found in these samples were compared with the concentration of fibronectin in 20 pregnancies complicated by diabetes. Mean plasma concentrations of fibronectin rose significantly through pregnancy and were significantly higher during delivery. A decrease in the concentrations was noticed on the third post partum day. An even more significant decrease of maternal plasma concentrations was noticed during cesarean section in normal pregnancies as compared to the concentrations found at the time of normal delivery. Of the diabetic group of women studied, higher concentrations of plasma fibronectin were found at the time of cesarean section than at the time of delivery. Maternal plasma concentrations of fibronectin were significantly greater than amniotic fluid and umbilical cord plasma concentrations.
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PMID:Plasma and amniotic fluid concentration of fibronectin during normal and diabetic pregnancy. 144 1

The pathogenesis of diabetic nephropathy relative to the changes in the glomerular extracellular matrices was investigated. Renal tissues from 10 diabetic patients were immunostained with antibodies directed against heparan sulfate proteoglycans (HS-PGs), laminin, type IV collagen and fibronectin. Seven patients were nephrotic and had advanced glomerulosclerosis with nodular lesion, while the other 3 had no renal manifestations or minor glomerular tissue alterations. Controls included kidneys removed from patients with renal tumors and specimens obtained by renal biopsy from patients with IgA nephropathy. Relationships among proteinuria, intensity of fluorescence and glomerular changes were studied. In diabetes 3 patients with minor glomerular lesions were found to have no changes in various components of extracellular matrices. A marked reduction in the intensity of staining with anti-HS-PG antibodies was observed in renal specimens from patients with nodular glomerulosclerosis and proteinuria, while a mild decrease in the intensity of fluorescence was observed in tissues stained with antilaminin antibodies. An increase compared to normal control sample findings in type IV collagen and fibronectin was observed in the mesangium of sclerosing glomeruli. No loss of HS-PG was observed in patients with IgA nephropathy. These results indicate that glomerular extracellular matrix HS-PG is lost in association with diabetic nephropathy; this loss results in alteration of the charge-selective properties of glomerular capillaries. This alteration may, in part, be the cause of the proteinuria associated with diabetic nephropathy.
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PMID:Heparan sulfate proteoglycans are lost in patients with diabetic nephropathy. 150 38

The effect of elevated glucose concentrations on the synthesis of basement membrane components was investigated in proliferating cultured porcine mesangial cells. Basement membrane associated heparan sulphate proteoglycan was determined by enzyme immunoassay with a specific antiserum recognizing the core protein of the heparan sulphate proteoglycan. When cells were exposed to increasing glucose concentrations up to 40 mmol/l, the heparan sulphate proteoglycan content was concomitantly decreased to 53% when compared to cells cultured under normal glucose concentrations or in the presence of 40 mmol/l sorbitol. The fibronectin content was essentially unchanged under these conditions. No significant effect of insulin on these basement membrane components was found. The results indicate that hyperglycaemia may be responsible for a decrease of mesangial heparan sulphate proteoglycan content in diabetes mellitus. This supports the view that loss of heparan sulphate proteoglycan may be an important step or even an initial event of mesangial alterations in diabetic glomerulopathy.
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PMID:Elevated glucose decreases the content of a basement membrane associated heparan sulphate proteoglycan in proliferating cultured porcine mesangial cells. 154 25

All the living molecules appear to suffer from the deleterious effects of aging, but the primary mechanisms of this inexorable evolution are still unknown. In the case of proteins, two major types of chemical reactions participate in the aging phenomena: 1) structural transformations induced by the addition of radicals by enzymic or non-enzymic reactions, 2) proteolytic cleavages. Among the reactions of the first group, the nonenzymatic glycation is the more generalized, not only in diabetic patients but also in non diabetic subjects. This glycation depends on the probabilities of encounters between circulating glucose molecules and free amino groups existing either at the N-terminal end of the polypeptide chains or on the lysyl side chains. These reactions are more frequent in the extracellular spaces and connective tissues because glucose circulates freely in these spaces, because the level of glucose is better controlled inside the cells (and even lower in diabetes mellitus), and finally because the proteins of these regions, such as the collagens, fibronectin and elastin, are relatively long lived, even if their life-span is really shorter than it was precedently believed. The binding of sugar residues to protein amino groups determines frequent modifications of structure that often make the molecule inactive. For instance, when a glucose unit binds to a lysyl radical located in the active center of an enzyme, it suppresses the activity of this enzyme. More generally, in the case of the connective tissue proteins that participate in complex supramolecular assemblies, the presence of additional radicals on some ponctual locations may interfere with the correct association of molecules. This is particularly true for basement membranes whose structure is impaired in diabetes. Glycation might also introduce abnormal cross-links between polypeptides or modify the antigenic power of some proteins and explain the formation of autoantibodies. Another property of glycated proteins is their reaction with oxygen leading to the formation of superoxide. The binding of a reducing sugar on an amino function is followed by an Amadori rearrangement that forms a ketol group. Ketols groups have the property to transmit electrons to molecular oxygen, and to forming superoxide radicals. Superoxide is capable of degrading only one protein: collagen, but it is also able to transform itself into hydrogen peroxide and hydroxyl radicals, which are far more toxic than O2-. The result of the formation of these oxygen free radicals from glycated proteins is the initiation of the degradation of several types of proteins, like the collagens.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Aging mechanisms of proteins]. 165 Dec 60

Advanced glycosylation endproducts (AGEs) are derived from the nonenzymatic addition of glucose to proteins. AGEs have been found to accumulate on tissue proteins in patients with diabetes, and their accumulation is thought to play a role in the development of diabetic complications. The finding that macrophages and endothelial cells contain AGE-specific receptors led us to examine whether mesangial cells (MCs) also possess a mechanism for recognizing and processing AGEs. Membrane extracts isolated from rat and human MCs were found to bind AGE-bovine serum albumin (BSA) in a saturable fashion, with a binding affinity of 2.0 +/- 0.4 x 10(6) M-1 (500 nM). The binding was specific for the AGE adduct, since AGE-modified collagen I and ribonuclease both competitively inhibited 125I-AGE-BSA binding to MC membranes, while the unmodified proteins did not compete. Binding of AGE proteins was followed by slow internalization and degradation of the ligand. Ligand blotting of MC membrane extracts demonstrated three distinct AGE-binding membrane proteins of 50, 40, and 30 kD. Growth of MCs on various AGE-modified matrix proteins resulted in alterations in MC function, as demonstrated by enhanced production of fibronectin and decreased proliferation. These results point to the potential role that the interaction of AGE-modified proteins with MCs may play in vivo in promoting diabetic kidney disease.
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PMID:Human and rat mesangial cell receptors for glucose-modified proteins: potential role in kidney tissue remodelling and diabetic nephropathy. 165 49

Cross-linking of cell matrix components by nonenzymatic glycosylation may contribute to diabetic glomerulopathy. We examined the effects of modification of matrix by nonenzymatic glycosylation on mesangial cell function. Matrix was generated by growing mesangial cells in tissue culture for 2 wk and removing the cells with a detergent cell-lysis solution. By indirect immunofluorescence and Northern-blot analysis, the remaining matrix contained laminin, fibronectin, and collagens type I and IV. The matrix was modified by incubation for 24 h with 50 mM glycolaldehyde, a highly reactive cross-linking nonenzymatic glycosylation product, or for 2 wk with 200 mM glucose-6-phosphate (G6P). Modification was carried out with or without equimolar aminoguanidine, an inhibitor of cross-link formation. Nonenzymatic glycosylation of the matrix by glycolaldehyde or G6P was confirmed by fluorometry and [14C]G6P incorporation and was prevented by aminoguanidine. [3H]thymidine incorporation for 24 h by mesangial cells plated onto unmodified or modified matrix was then performed. Modification of matrix had no effect on attachment of mesangial cells, determined 4 h after plating. Nonenzymatic glycosylation of matrix by glycolaldehyde or G6P significantly inhibited thymidine incorporation by mesangial cells. This effect was partially reversible by aminoguanidine. Aminoguanidine-modified matrix had no effect on thymidine incorporation. Thymidine-incorporation results were confirmed by direct cell counting. We conclude that modification of matrix by nonenzymatic glycosylation influences growth of mesangial cells, which could contribute to the mesangial abnormalities of diabetic glomerulopathy.
Diabetes 1991 May
PMID:Effects of nonenzymatic glycosylation of mesangial matrix on proliferation of mesangial cells. 170 34

The pathophysiology of peripheral circulatory disturbance in patients presenting with vibration syndrome was studied from the viewpoint of blood coagulation. Plasma levels of fibronectin (FN), vitronectin (VN), thrombin-antithrombin III complex (TAT), and alpha 2-plasmin inhibitor-plasmin complex (PIC) were measured in 23 subjects who showed no evidence of vibration-induced white finger [VWF(-) group] and in 24 patients who presented with VWF [VWF(+) group]. In the VWF(-) group, plasma FN concentrations were elevated but plasma TAT and PIC levels were within the normal ranges. In the VWF(+) group, plasma FN concentrations were normal but plasma TAT and PIC levels were significantly elevated. In both groups, plasma VN concentrations were similar to those in normal controls. For purposes of comparison, 32 patients presenting with diabetes mellitus were also studied. They were divided into 2 groups, 13 subjects who showed no evidence of angiopathy [complication(-) group] and 19 patients who presented with angiopathy [complication(+) group]. In the complication(+) group, plasma TAT and PIC concentrations were significantly elevated, as in the VWF(+) group. These results suggest that in vibration syndrome, vibration, cold stimulus, or other factors first injure the vascular endothelium, resulting in a rise in plasma FN, and that in the VWF(+) group, augmentation of coagulation and fibrinolysis induces a state of compensated disseminated intravascular coagulation (DIC).
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PMID:Activation of blood coagulation and fibrinolysis in vibration syndrome. 172 Jul 65

It could be demonstrated that plasma and tissue fibronectin (FN) increase with age. Some age dependent diseases as diabetes, osteoarthritis and Werner syndrome produce also an increase of tissue fibronectin biosynthesis. Plasma fibronectin decreases in diabetes and in breast cancer. Alternative splicing of the FN gene appears also to vary with age and in some related pathologies. Nutritional status and UV light also influence FN biosynthesis. It appears therefore that the determination of plasma FN and its isoforms as well as the study of tissue FN may be of interest for the study of chronological aging and related pathologies.
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PMID:[Fibronectin, aging and related pathologies]. 183 21


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