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)

The biosynthesis of collagen and fibronectin molecules by cultivated glomerular epithelial or mesangial cells was studied at confluency using radioactive proline or lysine as precursors. Collagen represented 0.5% of the total protein synthesized by the glomerular epithelial cells. About 60% of this collagenous protein were associated to the cell layer, whereas about 40% were secreted into the culture medium. Two major collagenous polypeptides were observed with apparent molecular weights of 185K and 170K, and were identified as two gene products of type IV procollagen. They exhibited ratios of 3- to 4-hydroxyproline, of total hydroxyproline to proline, and of hydroxylysine to lysine characteristic of type IV procollagen. They were degraded by bacterial collagenase. The patterns of peptides obtained after digestion of the 185K and 170K chains of this type IV procollagen with pepsin and V8 protease were identical to those obtained after digestion of type IV procollagen chains purified from a murine tumor (EHS sarcoma). Finally. a purified antibody to type IV collagen specifically immunoprecipitated the collagenous protein produced by the glomerular epithelial cells. By contrast, the mesangial cells synthesized about 5% of collagenous protein. 90% of this collagen were secreted into the cultured medium, whereas about 10% remained associated to the cell layer. Type I, III and IV procollagens were synthesized by the mesangial cells. Fibronectin was found in the medium and cell layer of both epithelial and mesangial cells. Fibronectin molecules were identified by their resistance to bacterial collagenase, their susceptibility to pepsin digestion, and their specific adherence to collagen. It was composed of disulfide-linked peptides of 220K daltons. The data therefore demonstrate that: (a) the glomerular epithelial and mesangial cells synthesize fibronectin molecules and type IV procollagen in vitro; (b) the cultivated mesangial cells also synthesize type I and III collagens. The implications of these findings in certain pathological circumstances, such as diabetes mellitus, are now being investigated.
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PMID:Synthesis of collagen and fibronectin by glomerular cells in culture. 732 12

High levels of von Willebrand factor (vWF) have been reported in diabetics with vascular complications, suggesting a role for this protein in the development of cardiovascular complications in non-insulin-dependent diabetes mellitus (NIDDM). Recently, a diet rich in monounsaturated fatty acids (MUFA) has been found to improve glycemic control and decrease diurnal blood pressure as compared with a high-carbohydrate (H-CHO) diet in NIDDM subjects. To study the impact of MUFA on the hemostatic system, we compared the levels of vWF, fibrinogen, fibronectin, and alpha 2-macroglobulin before and after 3 weeks on a high-MUFA (H-MUFA) diet and on an isocaloric H-CHO diet in 15 NIDDM subjects. In a crossover study, the patients were randomly assigned to a H-CHO diet (50% carbohydrate, 30% fat [10% MUFA]) or a H-MUFA diet (30% carbohydrate, 50% fat [30% MUFA]). Before and on the last day of the two diets, vWF, fibrinogen, fibronectin, and alpha 2-macroglobulin levels were measured. The H-MUFA diet caused a decrease in vWF from 1.31 +/- 0.08 to 1.13 +/- 0.08 U/mL (P < .004), whereas an unchanged level was observed after a H-CHO diet (1.19 +/- 0.11 v 1.25 +/- 0.11 U/mL, NS). The relative changes in vWF during 3 weeks on a H-MUFA and on a H-CHO diet attained -12.5% +/- 3.2% versus 5.7% +/- 3.5%, respectively (P < .0001). Furthermore, unchanged levels of fibrinogen, fibronectin, and alpha 2-macroglobulin were seen after usage of the two diets.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Decrease in von Willebrand factor levels after a high-monounsaturated-fat diet in non-insulin-dependent diabetic subjects. 752 26

Mother-fetus exchanges at the placental level are found to be altered in women affected by hypertensive or diabetic pregnancies following the onset of microenvironmental, circulatory, trophic or tissue disorders. Our aim was therefore to assess the alterations occurring within the umbilical cord, particularly its venous endothelial component and underlying smooth muscle layer, using transmission (TEM) and scanning electron microscopy (SEM) and immunohistochemical analyses. Immunohistochemical data appear to support the ultrastructural evidence for an activated state of these vascular structures, in both conditions (hypertension and diabetes). Furthermore, mainly during diabetic pregnancies, extracellular matrix molecules such as tenascin and fibronectin also quantitatively increase at the vein wall level. The umbilical cord seems to be a structure capable of responding actively to abnormal microenvironmental conditions which seriously threaten the health of the fetus and also the mother herself.
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PMID:The human umbilical vein in normal, hypertensive and diabetic pregnancies: immunomorphological and ultrastructural evidence. 754 29

Diabetic nephropathy is characterized by mesangial cell proliferation and expansion of the mesangial matrix. Insulin-like growth factor-1 (IGF-1) increases in the kidney early in experimental diabetes. The effect of IGF-1 on mesangial cell proliferation and synthesis of extracellular matrix (ECM) proteins was examined to test the hypothesis that IGF-1 stimulates mesangial cells to synthesize ECM proteins. ECM proteins were measured by immunoprecipitation after metabolic labeling of rat mesangial cells in culture. IGF-1 caused a 2.4-fold increase in mesangial cell proliferation as measured by 3H-thymidine incorporation. IGF-1 caused an increase in cellular laminin, fibronectin and type IV collagen, 46.8 +/- 15.4%, 31.3 +/- 11.4%, and 27.7 +/- 12.6% increase respectively compared to control cells. IGF-1 did not effect cellular type 1 collagen, decrease of 8.2 +/- 8.7%. There was a trend toward increased total protein synthesis by IGF-1, 36.5 +/- 2.5%. In summary, IGF-1 stimulates ECM component production by mesangial cells. Thus, IGF-1 has the capacity to mediate the histologic changes characteristic of diabetic nephropathy.
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PMID:Insulin-like growth factor-1 stimulates production of mesangial cell matrix components. 755 20

High ambient glucose concentration, linked to vascular complications in diabetes in vivo, modulates mRNA expression of fibronectin, collagen, tissue-type plasminogen activator, and plasminogen activator inhibitor and induces delayed replication and excess cell death in cultured vascular endothelial cells. To determine the role of high ambient glucose (30 mmol/l) in apoptosis, paired cultures of individual isolates of human umbilical vein endothelial cells (HUVECs) were exposed to both high (30 mmol/l) and low (5 mmol/l) concentrations of glucose for short-term (24, 48, and 72 h) and long-term (13 +/- 1 days) experiments. Incubation of HUVECs with high glucose for > 48 h increased DNA fragmentation (13.7 +/- 6.5% of total DNA, mean +/- SD) versus cultures kept in 5 mmol/l glucose (10.9 +/- 5.6%, P < 0.005), as measured by [3H]thymidine assays. Data were confirmed by apoptosis-specific fluorescence-activated cell sorter analysis of confluent HUVEC cultures, which displayed after long-term exposure to 30 mmol/l glucose a 1.5-fold higher prevalence of apoptosis than control cultures exposed to 5 mmol/l glucose (P < 0.005). In contrast, no increase in DNA fragmentation in response to 30 mmol/l glucose was seen for standardized cell lines (K 562, P 815, YT) and fibroblasts. Expression of clusterin mRNA, originally reported to be a molecular marker of apoptosis, was only slightly affected by short-term (24-h) high-glucose exposure but was significantly reduced after long-term incubation in 30 mmol/l glucose (82.2 +/- 13.8% of control) versus 5 mmol/l glucose, which questions the role of clusterin gene expression as a marker of apoptosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1995 Nov
PMID:High-glucose--triggered apoptosis in cultured endothelial cells. 758 31

The alpha 4 beta 1-integrin (CD49d, CD29) constitutively expressed on leukocytes regulates cell migration to inflammatory sites, cell activation, and development through its interactions with two alternate ligands, vascular cell adhesion molecule-1 (VCAM-1; CD106) expressed on cytokine-activated endothelium, dendritic and stromal cells, and the extracellular matrix protein fibronectin. Another alpha 4-integrin receptor, alpha 4 beta 7, expressed on leukocytes also binds VCAM-1 and fibronectin (FN), and controls homing to mucosal tissues through its interactions with mucosal vascular addressin MAdCAM-1. In vitro studies have shown that alpha 4-dependent cell adhesion is regulated by the activation state of the cell and by divalent cations. However, the existence and role of cells with different alpha 4 activation states in vivo have not been defined. Herein we show that a soluble ligand with the two N-terminal domains of human VCAM-1 fused to a human IgG1 constant region, VCAM-Ig, binds selectively to activated alpha 4-receptors on murine cells, such as those induced by Mn2+ in vitro. To determine whether the cells identified by VCAM-Ig were required under physiologic conditions, we assessed its anti-inflammatory effect. We show that VCAM-Ig is not bound to the majority of murine alpha 4+ cells after in vivo administration, yet it significantly delays the onset of adoptively transferred autoimmune diabetes. Thus, soluble VCAM-Ig can modify alpha 4-dependent disease progression, apparently by its selective action on cells with activated alpha 4-integrin receptors, thereby providing evidence for distinct alpha 4 activation states in vivo.
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PMID:Vascular cell adhesion molecule-Ig fusion protein selectively targets activated alpha 4-integrin receptors in vivo. Inhibition of autoimmune diabetes in an adoptive transfer model in nonobese diabetic mice. 760 69

Basement membrane thickening and mesangial expansion characterize the renal involvement in diabetes mellitus and precede any symptoms of renal dysfunction, e.g., albuminuria and changes in glomerular filtration rate. Since the morphological changes can only be diagnosed by biopsy, this study was designed to investigate whether the urinary excretion of renal extracellular matrix proteins might reflect the morphological alterations. To specify the extent of renal involvement in diabetes, the patients, type I as well as type II diabetics, were classified according to their urinary albumin excretion: normal albumin excretion below 30 micrograms/min, microalbuminuria from 30 to 300 micrograms/min, and overt albuminuria above 200 micrograms/min. Laminin, collagen IV, and fibronectin, all intrinsic components of the renal extracellular matrix, were determined in serum and urine by radioimmunoassay or enzyme-linked-immunosorbent-assay, respectively. The results are given as median values (mean). Additionally, the urinary fragment pattern of fibronectin was analysed qualitatively by immunoblotting. Laminin concentrations in serum and in urine did not change in diabetics. Collagen IV decreased in serum of patients with increased albumin excretion (controls: mean = 255 micrograms/l, normoalbuminuric patients: mean = 56 micrograms/l, microalbuminuric patients: mean = 52 micrograms/l, and patients with overt albuminuria: mean = 70 micrograms/l; alpha < 0.01) and increased in urine (controls, normoalbuminuric and microalbuminuric patients: not detectable, patients with overt albuminuria: mean = 5 ng/12 h; apha < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Extracellular matrix proteins as early markers in diabetic nephropathy. 762 93

Although increased plasma fibronectin (PF) levels have been found in diabetic patients with microalbuminuria, there is still controversy about its clinical implication for detecting early diabetic nephropathy. To evaluate the PF concentration as a possible marker for early diabetic nephropathy, three groups of sex-and age-matched patients were studied I) 22 insulin dependent diabetic (IDDM) patients with microalbuminuria (mean age +/- SEM: 23.3 +/- 3.6 years, mean urinary albumin excretion rate (AER) +/- SEM: 47.1 +/- 39.5 micrograms/min); II) 17 IDDM patients with normoalbuminuria (mean age: 23.4 +/- 4.4 years, mean AER: 7.8 +/- 2.1 micrograms/min) and III) 20 healthy control subjects (mean age: 22.6 +/- 4.1 years, mean AER: 6.7 +/- 2.1 micrograms/min). PF and urinary excretion of albumin were measured by an immunoturbidimetric method using commercially available kits (Boehringer Mannheim GMBH FRG, and Miles Lab., UK). The mean PF was significantly higher in the group with microalbuminuria (406.5 +/- 122.9 micrograms/ml) than in the group with normoalbuminuria (295.6 +/- 96.9 micrograms/ml, P < 0.01) or in the control group (299.54 +/- 105.5 micrograms/ml, P < 0.01). A weak positive correlation was found between PF and urinary albumin values (r = 0.35, P < 0.05). There were no significant correlations between PF and the other variables such as age, duration of diabetes, body mass index, arterial blood pressure, fasting blood glucose, fructosamine and HbA1 in the diabetic patients or in the control group. Our results suggest that the PF concentration could be a weak marker for early diabetic nephropathy. We cannot therefore use PF instead of microalbuminuria because there is only a weak correlation between PF and microalbuminuria.
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PMID:Can we use plasma fibronectin levels as a marker for early diabetic nephropathy. 762 76

Attachments of dorsal root ganglion (DRG) neurons from streptozotocin (STZ)-induced diabetic and normal C57BL mice to the following substrates were evaluated in vitro: a) poly L-lysine (PL), b) PL + type I collagen (CL-I), c) PL + type IV collagen (CL-IV), d) PL + laminin (LM) and e) PL + fibronectin (FN). After 6 h in culture, there was no significant difference in the average ratio of cells adhesive to PL between the diabetic (74.9%) and normal group of mice (75.6%). In the normal group, the addition of extracellular matrix (ECM) proteins such as CL-I, CL-IV, LM and FN to PL increased the ratios of cell attachment from 75.6% to nearly 90%. In the diabetic group, however, none of these proteins improved the attachment (the ratio changed from 74.9% to nearly 70%). Survival and neurite extension of attached cells after 48 h in culture were not different between the two groups. These results suggest that the cell-surface receptors, which enable DRG neurons to bind to the extracellular matrix proteins, are impaired by diabetes, resulting in being one of the causes of diabetic neuropathy.
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PMID:Diabetes impairs DRG neuronal attachment to extracellular matrix proteins in vitro. 763 2

To elucidate the mechanisms involved in the development of cutaneous fibrosis in scleredema adultorum, we studied a patient with long-standing scleredema who had no history of diabetes mellitus or preceding febrile illness. Histological examination of a biopsy specimen from involved forearm skin demonstrated marked thickening of the dermis and accumulation of mucin between collagen bundles. Increased levels of type I collagen mRNA, as evidenced by positive in situ hybridization signals with an alpha 1(I) procollagen cDNA were found in numerous fibroblasts throughout the dermis. The expression of several genes coding for proteins involved in the maintenance of connective tissue was examined by determining in vitro protein production and mRNA levels in fibroblasts from the affected skin. Total protein production, glucosamine incorporation and collagen synthesis, were elevated by 44-97% in scleredema fibroblasts, compared with fibroblasts from two healthy individuals. Levels of mRNAs for alpha 1(I) and alpha 1(III) procollagens and fibronectin were elevated in scleredema fibroblasts, whereas mRNA levels for the tissue inhibitor of metalloproteinase were unaltered compared with control cultures. The results suggest that fibroblasts from the involved skin in non-diabetic patients with scleredema may exhibit a biosynthetically activated phenotype, which persists for several years. These alterations are likely to be involved in the development of the cutaneous induration and thickening which is characteristic of this disease.
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PMID:Scleredema adultorum: case report and demonstration of abnormal expression of extracellular matrix genes in skin fibroblasts in vivo and in vitro. 766 81


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