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

In this chapter we have presented information on the development of large vessel damage in diabetes mellitus. A series of changes occur independent of the presence of atherosclerosis. The abnormalities include accumulation of PAS-positive material, laminin, fibronectin, type IV collagen and connective tissue with lack of acid mucopolysaccharides, and deposition of calcium. It is of particular interest that accumulation of PAS-positive material and lack of acid mucopolysaccharides are recognized as the histological markers of diabetic microangiopathy. These changes are in agreement with the hypothesis of a non-atherosclerotic large vessel damage, that is, diabetic macroangiopathy. From this standpoint the working hypothesis of a specific diabetic macroangiopathy should generate new ways to study the mechanism of the large vessel disease of diabetes over and above the traditional concept of classical atherosclerosis.
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PMID:Pathology of macrovascular disease. 297 20

This study was performed to evaluate the composition of the extracellular matrix of the mesangium in both diabetic and nondiabetic rats. Four groups of rats (n = 10 each) were studied. Nondiabetic rats were injected with saline (group 1) or insulin (3.5 U NPH daily) (group 2). Streptozocin-induced diabetic rats were similarly injected with saline (group 3) or insulin (group 4). Six weeks after initiation of study, glomerular diameter (micron) was increased in groups 2 (147 +/- 21), 3 (144 +/- 22), and 4 (150 +/- 7) compared with group 1 (104 +/- 12) (P less than .01). Glomerular hypertrophy was associated with an increase in the relative amount of mesangial matrix as determined by staining for fibronectin. By immunofluorescence microscopy (0-4+ scale), type I collagen antigen was not detected in the mesangium of any of the experimental groups. Staining for type V collagen and thrombospondin was similar between the experimental groups. Type III collagen antigen was not detected in the mesangium of control (group 1) or insulin-deficient diabetic rats (group 3); however, it was detected (2-3+) in the mesangium of both insulin-treated diabetic and nondiabetic rats (Mann-Whitney, P less than .01). Comparable intensity of staining (1+) for type IV collagen antigen was detected in the mesangium of animals from groups 1, 2, and 4; however, the staining intensity was markedly increased (3+) in insulin-deficient diabetic rats (group 3; Mann-Whitney, P less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1988 Dec
PMID:Phenotypic expression of collagen types in mesangial matrix of diabetic and nondiabetic rats. 305 64

Light and transmission electron microscopic study as well as immunohistochemical investigation were performed on three cases of light chain deposition disease (LCDD) with severe liver dysfunction. In two cases, the amount of light chain deposits in the liver was moderate and did not correlate with the severity of clinical and biological symptoms. Ultrastructural study demonstrated a collagenization of the Disse's space, with basement membrane-like material in association with light chain deposits. Immunohistochemical investigation showed a marked increase of collagen types I, III, and IV, as well as fibronectin and laminin in perisinusoidal space. This study suggests that collagenization of the Disse's space has a minor role in liver dysfunction. The analogy between kidney and liver lesions in diabetes and in LCDD is stressed, but the mechanism of this abnormal accumulation of matrix proteins remains unknown.
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PMID:Light chain deposition disease with liver dysfunction. 313 74

Raised levels of plasma fibronectin (PF), an alpha 2-glycoprotein produced by vascular endothelia, have been previously described in diabetic patients with retinopathy and overt nephropathy. The aim of this study was to investigate whether the presence of microalbuminuria is associated with increased PF concentrations. Twenty Albustix-negative diabetic outpatients with microalbuminuria [median albumin excretion rate (AER): 30.2 micrograms/min; range 12.1-194 micrograms/min] were compared with 58 sex- and age-matched patients without microalbuminuria (median AER 3.1 micrograms/min; range 0.8-12 micrograms/min) and 34 control subjects (median AER 2.8 micrograms/min; range 0.8-12.1 micrograms/min). Mean PF was significantly higher in the group with microalbuminuria (406.7 +/- 85.5 micrograms/ml) than in the group without it (325.3 +/- 76.5 micrograms/ml or in control subjects (334.5 +/- 76 micrograms/ml; P less than .05). PF increase associated with microalbuminuria was independent of the presence of retinopathy. Furthermore, in the whole group of diabetic patients, PF was significantly correlated with AER (r = .33; P = .003). Such correlation also remained significant (P = .0002) after covariance analysis by a stepwise discriminant procedure taking into account age, duration of disease, sex, blood pressure, body weight, therapy, and HbA1. In conclusion, PF increase is associated with microalbuminuria independent of the other considered variables; its role as a possible marker for early diabetic nephropathy remains to be fully clarified.
Diabetes Care
PMID:Increased plasma fibronectin concentration in diabetic patients with microalbuminuria. 320 68

Recent concepts on the mechanisms of aging of extracellular matrix (EM) are reviewed as well as its involvement in age-associated diseases. Cell differentiation, histogenesis and organogenesis can be analyzed in terms of the program of the biosynthesis of EM macromolecules during development, maturation and aging. The most important biological role of EM is the integration of cells in tissues, of tissues in organs and of organs in the whole organism. EM can directly influence cell behavior through the contact between EM and the genome mediated by structural glycoproteins (fibronectin, laminin, elastonectin, etc.) interacting with other EM macromolecules (collagen, proteoglycans, elastin) and the cytoskeleton by trans-membrane receptors (integrins). Most age-associated diseases exhibit a deviation (qualitative or quantitative) from the normal program of EM biosynthesis. Three examples are analyzed in some detail: atherosclerosis, diabetes and malignant tumors. The degradation of elastic fibers catalyzed by cellular elastase-type enzymes is observed in atherosclerosis and also in emphysema and skin aging. Several of these enzymes were isolated and characterized from platelets, fibroblasts, smooth muscle cells and lipoproteins. The biosynthesis of some of them increases with age and facilitates cell migration. Plasma fibronectin increases with age exponentially. This increase is absent or strongly attenuated in diabetes and some cancers. Tissue fibronectin increases in diabetes, Werner syndrome and in the peritumoral desmoplastic reaction while most tumor cells can no more retain fibronectin on their membrane facilitating their movement in the organism. These examples demonstrate the importance of the study of cell matrix interactions for gerontology.
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PMID:Aging of the extracellular matrix and its pathology. 328 58

Immune complex-mediated injury has been postulated to contribute to diabetic microangiopathy. To test this hypothesis, immune complex disease was induced in both insulin-deficient (I-) and insulin-treated (I+) rats with streptozocin-induced diabetes mellitus (DM), and the rats were compared with their respective controls. Heymann nephritis (HN), an animal model of membranous nephropathy, was induced in rats by immunization with proximal renal tubular brush border antigen. In addition to the homogeneous mesangial deposits of IgG that developed in diabetic rats, diabetic rats with immune injury also developed immune deposits of IgG and tubular antigen. Diabetic animals with Heymann nephritis developed more intense granular mesangial and capillary wall immune deposits, detected by immunofluorescence (ranked-sums test, P = .002) and electron microscopy. Mesangial immune deposits were associated with mesangial hypercellularity, determined by counting nuclei per glomerular cross section. Diabetic animals with immune injury had an increased number of nuclei (DM, I-, HN: 70 +/- 4; DM, I+, HN: 65 +/- 3) compared with animals with only Heymann nephritis (55 +/- 4) or only diabetes [DM, I-: 52 +/- 4; DM, I+: 54 +/- 3 (mean +/- SE); P less than .05, ANOVA]. An increase in the accumulation of mesangial matrix in diabetic animals with Heymann nephritis was also apparent by light microscopy and immunofluorescence staining of the mesangium for fibronectin. Insulin treatment and control of hyperglycemia did not prevent the development of these changes. Animals with only Heymann nephritis had lesser amounts of immune deposits, which were limited to the subepithelial space and not associated with structural alterations of the mesangium.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1987 Nov
PMID:Accelerated glomerulosclerosis in diabetic rats with immune complex injury. 331 53

We examined neutrophil adherence to bovine aortic endothelial cells in 26 patients with diabetes compared with age- and sex-matched controls. The adherence of chromium 51-labeled neutrophils from patients with diabetes in the basal state and after incubation with phorbol myristate acetate (PMA) but not N-formyl-methionyl-leucyl-phenylalanine (FMLP) was decreased significantly. A subset of 16 of 26 patients demonstrated highly significant decreases in basal adhesion. No significant correlation was found between defective adherence and metabolic control as assessed by plasma glucose level (range 44 to 508 mg/dl) and hemoglobin A1 level (range 7.7% to 17.1%) at the time of study. Plasma from patients with diabetes increased adherence of both diabetic and control neutrophils in the basal state. The adherence-augmenting factor in diabetic plasma was found to be nonfilterable and partially heat labile and to manifest the characteristics of a protein. The adhesive effects of diabetic plasma were mediated through alterations in endothelium rather than neutrophils. Diabetic neutrophil aggregation induced by PMA, FMLP, and calcium ionophore was normal in all patients examined, regardless of the aggregating agent used. Fibronectin release in the basal state and after stimulation with FMLP was found to be comparable in diabetic and control neutrophils. These studies demonstrated intrinsic adhesive dysfunction of diabetic neutrophils and a factor or factors in diabetic plasma that enhanced adherence to endothelium. These cellular and humoral factors may act together to prevent tissue emigration of neutrophils and may contribute to the pathogenesis and susceptibility of infection in diabetes.
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PMID:Neutrophil adhesive dysfunction in diabetes mellitus; the role of cellular and plasma factors. 334 42

Although the degree of hyperglycemia is a powerful and independent risk factor for diabetic microvascular disease, it has not been established if and how high glucose per se can induce the typical lesions of microangiopathy. We have investigated in human vascular endothelial cells the expression of messenger RNA (mRNA) for collagen type IV and fibronectin, the two glycoproteins characteristically increased in diabetic basement membranes. In 12 confluent primary cultures exposed for 11 +/- 1 d (mean +/- SD) to 30 mM glucose and exhibiting cell number and thymidine incorporation similar to control cultures, the levels of collagen IV and fibronectin mRNA were, respectively, 238 +/- 140 and 221 +/- 231 percent of control (P less than 0.01). The effects of high glucose were selective (the levels of collagen I and c-myc mRNA remained unchanged), independent of the proliferative activity of the cultures and of the plating substratum, and maintained throughout multiple passages. However, several days of exposure to high glucose were required before their appearance. These observations establish that high glucose is a perturbation sufficient to mimic the effects of diabetes on the regulation of basement membrane components and propose that modifications in gene expression may pertain to the chain of events leading to diabetic angiopathy.
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PMID:Increased expression of basement membrane components in human endothelial cells cultured in high glucose. 340 25

Adhesion of bovine endothelial cells on fibronectin and collagen before and after nonenzymatic glycation in vitro has been studied. Nonenzymatic glycation of these proteins reduced their ability to bind endothelial cells. Furthermore, nonenzymatically glycated fibronectin failed to bind to normal and nonenzymatically glycated gelatin and to fibrin. So gelatin and fibrin Sepharoses can be used to separate highly glycated fibronectins from fibronectins with a low degree of nonenzymatic glucose substitution. Sodium dodecylsulfate polyacrylamide gel electrophoresis did not demonstrate a covalent cross-link between nonenzymatically glycated fibronectins. These results present further evidences for the role of nonenzymatic glycation of proteins in the development of vascular complications in long-term diabetes and of atherosclerosis.
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PMID:Diminished adhesion of endothelial aortic cells on fibronectin and collagen layers after nonenzymatic glycation. 340 68

The nonenzymatic glycation of basement membrane proteins, such as fibronectin and type IV collagen, occurs in diabetes mellitus. These proteins are nonenzymatically glycated in vivo and can also be nonenzymatically glycated in vitro. After 12 days of incubation at 37 degrees C with 500 mM glucose, purified samples of human plasma fibronectin and native type IV collagen showed a 13.0- and 4.2-fold increase, respectively, in glycated amino acid levels in comparison to control samples incubated in the absence of glucose. Gelatin (denatured calfskin collagen) was glycated 22.3-fold under the same conditions. Scatchard analyses were performed on the binding of radiolabeled fibronectin to gelatin or type IV collagen. It was found that there is a 3-fold reduction in the affinity of fibronectin to type IV collagen due to the nonenzymatic glycation of fibronectin. The dissociation constant (KD) for the binding of control fibronectin to type IV collagen was 9.6 X 10(-7) M while the KD for glycated fibronectin and type IV collagen was 2.9 X 10(-6) M. This was similar to the 2.7-fold reduction in the affinity of fibronectin for gelatin found as a result of the nonenzymatic glycation of fibronectin (KD of 4.5 X 10(-7) M for the interaction of control fibronectin with gelatin vs. KD of 1.2 X 10(-6) M for the interaction of nonenzymatically glycated fibronectin with gelatin). The molecular association of control fibronectin or its glycated counterpart with [3H]heparin was also determined. Scatchard analyses of this interaction showed no difference between control fibronectin and glycated fibronectin in [3H]heparin binding.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Decreased interaction of fibronectin, type IV collagen, and heparin due to nonenzymatic glycation. Implications for diabetes mellitus. 356 52


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