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

Basement membranes support epithelial and endothelial cells, prevent the passage of proteins, and generate histologically distinct compartments in the body. Basement membranes contain a number of components, only some of which have been isolated and characterized. These include type IV collagen, heparan sulfate proteoglycan, laminin, entactin, and fibronectin. Some components, such as bullous pemphigoid antigen and Goodpasture antigen, are present only in specific tissues, such as the skin or the kidneys. Alterations in basement membranes are associated with various diseases. For example, metastatic cells are able to attach to basement membranes and to degrade them. Such interactions with basement membranes underlie the ability of these cells to penetrate tissues and to spread in the body. In diabetes, basement membranes are thickened but are more porous, which is possibly due to a decreased amount of heparan sulfate proteoglycan. Basement membranes are also the site of immunopathologic disorders.
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PMID:Structure, function, and pathology of basement membranes. 635 Aug 56

We have measured plasma von Willebrand factor (VWF) as the factor VIII-related antigen, plasma fibronectin, and two of the serum somatomedins, insulin-like growth factor I (IGF I) and IGF II, in 51 diabetic patients and 25 nondiabetic control subjects. VWF was significantly higher in the diabetic group than in the controls (173 +/- 9% SEM versus 101 +/- 9%, P less than 0.001), as has been reported by others. However, within the diabetic group there was no significant difference in VWF between those patients without retinopathy, those with background or proliferative retinopathy, or those with macular edema. There was also no difference in VWF between the diabetic subjects with and those without proteinuria. These results rule against a previously advanced hypothesis that the increase in VWF in patients with diabetes is secondary to microangiopathy. No significant difference was observed in fibronectin, IGF I, or IGF II between the diabetic and control groups, between the diabetic group without retinopathy and the retinopathic subgroups, and between the diabetic subjects with and without proteinuria. In the diabetic patients, there was no correlation between diabetic control as assessed by glycosylated hemoglobin and glycosylated serum protein, and the plasma levels of VWF, fibronectin, IGF I, or IGF II. The results of this study strongly suggest that neither plasma VWF, fibronectin, IGF I, nor IGF II plays an important primary role in the pathogenesis of diabetic microvascular disease, although one or more of these factors might play a permissive role.
Diabetes 1984 Feb
PMID:Von Willebrand factor (VIII R:Ag), fibronectin, and insulin-like growth factors I and II in diabetic retinopathy and nephropathy. 636 66

Fibronectin is present in tissues and also in body fluids (plasma). Both forms were studied in normal controls, diabetics and cancer patients; both of these diseases show an age-dependent increasing trend. Age-dependent variations were shown to occur for both forms of fibronectin. Plasma fibronectin increases exponentially with age in a normal population. This increase is strongly attenuated or absent in diabetics and in mammary cancer patients. On the contrary, tissue fibronectin increases in diabetic skin. In mammary cancer fibronectin disappears from the tumor cell membranes but increases in the peritumoral stroma. The above modifications may be attributed to increased protease activity in tumour tissue and also to the possibility of an increased retention of plasma fibronectin in diabetic skin and peritumoral stroma, both tissues exhibiting a modification of intercellular matrix biosynthesis which does involve the increased production of retention sites of fibronectin. An increased local synthesis in both tissues may also occur. The above results are confronted with those reported by other authors and support the contention that plasma and tissue fibronectins undergo age-dependent modifications which may be seriously perturbed in diabetes and cancer.
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PMID:Modifications of fibronectin in age-related diseases: diabetes and cancer. 637 13

Plasma fibronectin was determined by laser immunonephelometry in controls (90 women, 66 men) and 167 diabetic patients between 10 and 60 years of age, 72 insulin-dependent males, 45 insulin-dependent females, 29 noninsulin-dependent males and 21 non-insulin-dependent females. The distribution and intensity of immunofluorescent tissue fibronectin were also studied in the patients using skin biopsies. The diabetic patients had a significantly lower plasma fibronectin level than the controls of the same age-groups and did not exhibit the strong age-dependent increase found for controls. This was true for both females and males, and especially pronounced for the insulin-dependent male patients below 45 years. The duration (less or more than 10 years), and control of diabetes (judged by the glycosylated hemoglobin A1C levels, presence or absence of retinopathy), had a lesser influence on plasma fibronectin levels, although the duration of the disease tended to increase plasma fibronectin levels. Tissue fibronectin appeared to increase as estimated by the intensity and distribution of immunofluorescence in the papillary dermis, and in vascular and dermo-epidermal basement membranes, suggesting an inverse variation of tissue and plasma fibronectin in diabetes.
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PMID:Plasma and tissue fibronectin in diabetes. 638 77

The immunohistopathology of the intrinsic basement membrane-associated antigens were examined in diabetic nephropathy. In early and moderate stages of disease there was polyantigenic expansion of all the intrinsic components of mesangium, glomerular basement membrane (GBM), and tubular basement membrane (TBM) assessed by polyclonal antisera to collagen types IV and V, laminin, and by monoclonal antibodies to type IV collagen and fibronectin and to four other intrinsic components of normal renal extracellular matrices (MBM10, 11, 12, and 15). In the mesangium the first intrinsic antigens to increase were fibronectin and type V collagen. In late stages of disease, there was a diminution in the mesangium of all of these antigens with the exception of type V collagen, which persisted. Additionally, antigens appeared in the mesangium, recognized by MBM11 and MBM15, which are normally present in fetal but not adult mesangial regions. Similarly, in the GBM in late stages of disease, there was a decrease in all of the antigens, except for a persistence of the antigen recognized by MBM15. However, in TBM all of the antigens assessed increased in early, moderate, and severe disease. These studies document the complexity of polyantigenic alterations in the development of diabetic nephropathy.
Diabetes 1983 May
PMID:Polyantigenic expansion of basement membrane constituents in diabetic nephropathy. 640 Jun 67

Plasma fibronectin and serum thyroid parameters were determined in 6 hyperglycemic nonketoacidotic patients (HNK) and 12 subjects with diabetic ketoacidosis (DKA). The DKA patients showed a marked increase in both plasma fibronectin and serum T3 over 5 days of insulin treatment [175.2 +/- 18.1% (+/- SEM) and 208.7 +/- 17.6% of initial values respectively], while these parameters did not change in the HNK patients despite equivalent control of diabetes. Serum rT3 levels declined, as expected, to 65.8 +/- 10.9% of the initial values in the DKA patients, but did not change in the HNK patients. There was a significant positive correlation between changes in plasma fibronectin and serum T3 values in the DKA patients (r = 0.5; P less than 0.005). Other reports have shown a decrease in plasma fibronectin concentrations in fasted patients, a well known low T3 state; therefore, the association between changes in plasma fibronectin and serum T3 values may be a widely observed phenomenon. The parallel changes in fibronectin and T3 may reflect alterations in the metabolic state of these patients. The precise nature of the relationship between changes in fibronectin and T3 concentrations requires additional investigations.
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PMID:Rapid increase in both plasma fibronectin and serum triiodothyromine associated with treatment of diabetic ketoacidosis. 640 48

We examined the effect of nonenzymatic glycosylation on the ability of fibronectin, an extracellular glycoprotein that interacts with cell surfaces and matrix components, to bind to collagen and heparin. Nonenzymatic glycosylation was accomplished by incubation of the protein with glucose, both cold and [14C]-labeled, and documented by measurement of ketoamine-bound carbohydrate with the thiobarbituric acid assay. Effect on binding was assessed with affinity chromatography on heparin-Sepharose and gelatin-Sepharose, and with an in vitro assay that detects complexation of fibronectin with [3H]-heparin. Glycosylated fibronectin did not bind to these immobilized matrix components, and in vitro binding of the glycosylated protein was reduced compared with that of nonglycosylated fibronectin. Inhibition of heparin binding in the in vitro assay was observed even with levels of glycosylation about threefold those of control, which is comparable to the degree of glycosylation determined in fibronectin isolated from plasma of two patients with uncontrolled diabetes. The findings indicate that nonenzymatic glycosylation of fibronectin inhibits its binding to connective tissue components, and suggest that this process contributes to faulty integrity of extracellular matrices in diabetes.
Diabetes 1984 Oct
PMID:Inhibition of fibronectin binding to matrix components by nonenzymatic glycosylation. 647 61

The high incidence of thrombosis in inflammatory states and previous reports of increased adhesion of erythrocytes to endothelial cells in diabetes mellitus and sickle cell anemia prompted us to study the effect of fibrinogen and fibronectin on erythrocyte-endothelial interactions. Purified human fibrinogen enhanced erythrocyte adhesion in a concentration-dependent fashion. Erythrocytes from normal subjects, diabetics, and patients with sickle cell anemia were studied. The ratio between the adhesion of normal red cells in a 4 gm/L fibrinogen to adhesion in buffer without fibrinogen was 3.6 (p less than 0.001). Fibronectin also increased red cell adhesion but the effect was less than that of fibrinogen. The addition of fibronectin to fibrinogen limited the enhancing effect of fibrinogen, although the effect of the mixture was greater than that of fibronectin alone (p less than 0.05). Anti-von Willebrand factor and antifibronectin, which react with endothelial cells, also produced an increase in erythrocyte adhesion. The potentiation of adhesion by fibrinogen was also seen in experiments using red cells from patients with sickle cell anemia or diabetes mellitus. These observations provide possible mechanisms for the involvement of plasma proteins in vascular occlusive diseases.
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PMID:Fibrinogen, a modulator of erythrocyte adhesion to vascular endothelium. 685 27

In contrast to previous studies of diabetic humans and animals, which reported unchanged or depressed function, reticuloendothelial system (RES) hyperphagocytosis of colloidal carbon, 125I-albumin microaggregates, and 125I-fibrin monomers were observed in rats as early as 14 days after the induction of diabetes with streptozotocin (STZ). The fact that enhanced phagocytosis by RE macrophages was prevented by chronic insulin replacement therapy indicates that the diabetic internal environment of hyperglycemia and hypoinsulinemia was perhaps responsible for the observed changes. Experiments involving organ localization of intravenously administered particles, perfusion of isolated livers, and microscopic examination of the liver all suggested that increased Kupffer cell activity was the primary event in RES hyperphagocytosis by STZ-diabetic rats. Both hypertrophy and hyperplasia of Kupffer cells were apparent in livers of STZ-diabetic animals as evidenced by photomicrographs and hepatic cell quantification. Plasma fibronectin, which binds fibrin monomers to RE macrophages before phagocytosis, was significantly decreased in the circulation of STZ-diabetic rats, but the level of cell-associated fibronectin was not measured. Renal localization of urea-soluble 125I-fibrin monomers exceeded splenic and pulmonary uptake in normal control rats and was enhanced in animals with STZ-diabetes. Changes in fibronectin levels, fibrin monomer localization, and Kupffer cell size and numbers in experimental diabetes in rats may have implications for the pathogenesis of vascular disease involving phagocytic mesangial and foam cells in diabetic humans.
Diabetes 1982 Feb
PMID:Reticuloendothelial hyperphagocytosis occurs in streptozotocin-diabetic rats. Studies with colloidal carbon, albumin microaggregates, and soluble fibrin monomers. 715 27

The large vessel disease develops slowly and progressively among most diabetics. According to the concept of a specific diabetic macroangiopathy, the alterations in the large vessels are part of the general diabetic angiopathy and are different from the spotty atherosclerosis. This hypothesis proposes that the changes develop a consequence of the metabolic situation in diabetes. The concept is based on epidemiologic, clinical, and patho-anatomical observations. A model of large-vessel disease in diabetes is briefly described. Diabetic serum causes proliferation of the aortic myomedial cells in culture. Growth hormone causes a similar proliferation. Type 1 procollagen and fibronectin elaboration is enhanced by diabetic serum. The same effect has been found with growth hormone. Insulin treatment in experimental diabetes prevents the proliferation of arterial myomedial cells in the coronary arteries. The presented data are compatible with the concept of a diabetic macroangiopathy distinct from atherosclerosis.
Diabetes 1981
PMID:Diabetic macroangiopathy and growth hormone. 729 69


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