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

Untreated diabetes reduces wound strength: a concomitant reduction in collagen deposition has been found in cutaneous wounds but not in intestinal anastomoses. This raises the question if collagen synthesis in fibroblasts from skin and intestine reacts differently to the diabetic state. Fibroblast lines were established from healthy rat skin and ileum. Diabetic rat serum was collected from hyperglycaemic rats 3 days after intravenous injection of streptozotocin (200 mg/kg). Fibroblast cultures were grown to confluency in foetal calf serum and maintained in various concentrations of glucose, insulin, normal or diabetic rat serum. Collagen synthesis was measured by incorporation of [3H]-proline into Collagenase-Digestible-Protein. Collagen synthesis in fibroblasts from both skin and ileum was not affected by increasing glucose concentrations. Insulin strongly and specifically stimulated collagen synthesis in skin fibroblasts whereas in ileum fibroblasts only a nonspecific increase of total protein synthesis was observed. In skin fibroblasts, diabetic rat serum stimulated collagen synthesis to a significantly lesser extent than normal rat serum, whereas in ileum fibroblasts stimulation by serum was far less explicit and no difference was observed between normal and diabetic serum. The fact that ileum fibroblasts respond less strongly to culture in diabetic serum than skin fibroblasts may explain our prior finding that would collagen accumulation in intestinal anastomoses is virtually unaffected during diabetes and supports the existence of tissue-specific healing responses.
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PMID:Collagen synthesis in rat skin and ileum fibroblasts is affected differently by diabetes-related factors. 1019 15

The formation of advanced glycation end-products plays a central role in the progressive deterioration of tissues with age, a process that is accelerated in diabetes. Collagen in addition to providing structure and tensile strength to tissues also provides a dynamic matrix for cells to interact with, and due to its long-lived nature is particularly susceptible to modification with age and disease. We have recently identified methylglyoxal as a key intermediate in this process, reacting predominantly with arginine residues to form imidazolone compounds. We therefore postulated that modification of RGD sequences in collagen with methylglyoxal would interfere with crucial cell-matrix interactions. To investigate this concept we studied the interaction of two cell lines, MG63 and HT1080, with collagen modified to varying degrees with respect to arginine. Adhesion and subsequent spreading of both cell lines was significantly decreased by minimal methylglyoxal modification leading to the conclusion that such modification of collagen severely inhibits cell matrix interactions, most likely via the loss of specific arginine residues involved in integrin mediated cell attachment. This is the first demonstration that methylglyoxal modification of collagen can affect cell-matrix interactions and introduces a possible mechanism by which some of the deleterious changes in tissues with age and disease are occurring.
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PMID:The effect of advanced glycation end-product formation upon cell-matrix interactions. 1040 38

This study was undertaken to examine the effect of fibrin stabilizing factor (F.XIII) on healing of bone defects in normal and uncontrolled diabetic rats. Eighty rats were divided into two groups: group I (diabetic) and group II (non-diabetic) (40 rats each). Diabetes was induced in group I using streptozotocin. Both groups were divided into two subgroups, control and experimental (20 rats each). Bone defect was created in the mandible. Rats in the experimental subgroups were injected with F.XIII, while those of the control groups were injected with saline (F.XIII solvent). Animals were killed at varying intervals and tissue sections stained with hematoxyline and eosin and Van-Gieson stains were examined. Differences in collagen deposition and bone formation were compared in both control and experimental groups. Collagen deposition was evident and appeared more oriented in diabetic rats treated with F.XIII, and signs of bone deposition started in the experimental group earlier than in the control group. On the other hand, F.XIII did not significantly affect healing in non-diabetic rats. It is concluded from these results that F.XIII may enhance early stages of bone healing in uncontrolled diabetic rats.
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PMID:The effect of fibrin stabilizing factor (F.XIII) on healing of bone defects in normal and uncontrolled diabetic rats. 1041 1

To analyze possible early abnormalities in bone resorption in type 1 diabetes mellitus the urinary excretion of the collagen crosslinks pyridinoline and deoxypyridinoline was evaluated by immunoassay in 26 prepubertal diabetic patients (mean age 7.8 +/- 1.6 years, mean duration 3.0 +/- 1.1 years) and 46 healthy children (age 8.3 +/- 1.3 years). Relationships with growth parameters (height-standard deviation score, body mass index and height velocity during the year preceding the study) and metabolic control were sought. Longitudinal and ponderal growth was normal in diabetic children. Urinary collagen crosslink excretion was 88.4 +/- 25 nmol/mmol creatinine (median 86, range 44-146) in diabetic patients and 65.6 +/- 19 nmol/mmol creatinine (median 61, range 32-108) in controls (p = 0. 0002). It was positively influenced by diabetic status (beta = 20.5) and negatively by age (beta = -6.41), controlling by sex and BMI (p = 0.0001). A positive correlation was found between collagen crosslinks and blood glucose (r = 0.48, p = 0.01) or HbA1c levels (r = 0.44, p = 0.02) evaluated at the time of the study, while no significant correlation was found with the mean HbA1c values assessed in the last year or throughout the whole duration of diabetes. Collagen crosslink excretion was significantly increased in patients who presented worsening of their metabolic control in the last 3 months. No relationship was found with the duration of disease or growth parameters. In conclusion, the elevated urinary excretion of collagen crosslinks in diabetic children indicates that bone resorption may be disturbed. Poor metabolic control influences the increased rate of bone resorption and may expose growing diabetic patients to a risk of bone loss.
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PMID:Increased urinary excretion of collagen crosslinks in type 1 diabetic children in the first 5 years of disease. 1047 18

The accelerated formation of advanced glycation end-products (AGEs) due to elevated glycemia has repeatedly been reported as a central pathogenic factor in the development of diabetic microvascular complications. The effects of a novel inhibitor of AGE formation, NNC39-0028 (2,3-diaminophenazine), and a breaker of already formed AGE cross-links, N-phenacylthiazolium bromide (PTB), were investigated in streptozotocin-diabetic female Wistar rats. Diabetes for 24 weeks resulted in decreased tail collagen pepsin solubility, reflecting the formation of AGE cross-linking. Collagen solubility was significantly ameliorated by treatment with NNC39-0028, whereas PTB had no effect. Increased urinary albumin excretion (UAE) in diabetic rats was observed in serial measurements throughout the study period, and was not reduced by any treatment. Vascular dysfunction in the eye, measured as increased clearance of 125I-albumin, was induced by diabetes. NNC39-0028 did not affect this abnormality. This study demonstrated a pharmacological inhibition of collagen solubility alterations in diabetic rats without affecting diabetes-induced pathophysiology such as the increase in UAE or albumin clearance. Treatment with PTB, a specific breaker of AGE cross-links, had no effects in this study.
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PMID:Effects of advanced glycation end-product inhibition and cross-link breakage in diabetic rats. 1095 16

Insulin dependent diabetes mellitus, marked by high blood glucose levels and no insulin secretion, is associated with decreased bone mass and increased fracture rates. Analysis of bone histology suggests that osteoblast phenotype and function are influenced by diabetes. To determine if elevated extracellular glucose levels could directly influence osteoblast phenotype we treated mouse osteoblasts, MC3T3-E1 cells, with 22 mM glucose and analyzed osteoblast gene expression. Collagen I mRNA levels significantly increased while osteocalcin mRNA levels decreased 24 h after the addition of glucose. Expression of other genes, actin, osteopontin, and histone H4, was unaffected. Effects on collagen I expression were seen as early as 1 h after treatment. c-Jun, an AP-1 transcription factor involved in the regulation of osteoblast gene expression and growth, was also modulated by glucose. Specifically, an increase in c-jun expression was found at 1 h and maintained for 24 h following glucose treatment. Treatment of osteoblasts with an equal concentration of mannitol completely mimicked glucose treatment effects on collagen I and c-jun expression, demonstrating that osmotic stress rather than glucose metabolism is responsible for the effects on osteoblast gene expression and phenotype. Additional studies using staurosporine and Ro-31-8220 demonstrate that protein kinase C is required for the glucose up regulation of collagen I and c-jun. Taken together, our results demonstrate that osteoblasts respond to increasing extracellular glucose concentration through an osmotic response pathway that is dependent upon protein kinase C activity and results in upregulation of c-jun and modulation of collagen I and osteocalcin expression.
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PMID:Extracellular glucose influences osteoblast differentiation and c-Jun expression. 1096 57

Collagen vascular diseases commonly affect the heart; cardiovascular events are the major cause of mortality in people with these diseases. A striking feature of the cardiac involvement in individuals with systemic lupus erythematosus (SLE) and rheumatoid arthritis is aggressive and accelerated atherosclerosis; women with SLE in the 35- to 44-year-old age group are more than 50 times more likely to suffer myocardial infarction than are matched controls. Traditional risk factors contribute to the accelerated atherosclerosis, but cannot explain the extent of risk. It is possible that the inflammatory process, which is similar to the inflammatory process in atherosclerosis, pays a critical pathophysiologic role. It is critically important to identify the presence of traditional cardiovascular risk factors (eg, tobacco usage, hypertension, hypercholesterolemia, diabetes, homocysteinemia), and to modify these to secondary prevention targets. Cardiac valvular disease is common in individuals with SLE and rheumatoid arthritis; its presence should be anticipated and subacute bacterial endocarditis prophylaxis precautions initiated. Cardiac autonomic neuropathy and conduction disturbances are common in people with heart disease related to systemic sclerosis and human leukocyte antigen B27; these patients should be monitored carefully for evidence of dysrhythmias.
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PMID:Cardiovascular Complications of Collagen Vascular Disease. 1185 77

Collagen-induced arthritis (CIA) is a useful model for dissecting the genetic patterns underlying susceptibility to rheumatoid arthritis (RA) and related chronic/inflammatory autoimmune diseases. CIA exhibits three phenotypes characteristic of autoimmune disease pathogenesis: abnormal levels of immune reactivity to self antigens; chronic inflammation of target organs expressing that specific autoantigen; activation and direct participation of invading mononuclear cells and resident tissue fibroblasts in organ damage. Over 25 different quantitative trait loci (QTL) regulating arthritis severity and autoantibody in rats with CIA are mapped. QTL-congenic strains show that certain CIA-QTLs can modulate arthritis independently These monogenic models are proving to be highly informative for fine mapping and function studies, revealing gender effects and evidence of gene clusters. Recent genome scans of RA populations identified RA-susceptibility loci in chromosome regions homologous to rat chromosomal segments housing CIA-QTLs. Also, CIA-QTLs frequently co-localize with susceptibility QTLs mapped in other rat arthritis models induced with non-immunogenic adjuvant oils and/or in rat autoimmune models of multiple sclerosis and diabetes. Common autoimmunity genes and inflammation genes important to several human diseases are likely being detected in the various rat disease models. Continued dissection of the genetic underpinnings of rat arthritis models should provide candidate genes for investigation in human patients and lead to a clearer understanding of the complex genetics of RA.
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PMID:Genetic analysis of collagen-induced arthritis in rats: a polygenic model for rheumatoid arthritis predicts a common framework of cross-species inflammatory/autoimmune disease loci. 1208 11

Protein kinase C (PKC) beta isoform activity is increased in myocardium of diabetic rodents and heart failure patients. Transgenic mice overexpressing PKCbeta2 (PKCbeta2Tg) in the myocardium exhibit cardiomyopathy and cardiac fibrosis. In this study, we characterized the expression of connective tissue growth factor (CTGF) and transforming growth factor beta (TGFbeta) with the development of fibrosis in heart from PKCbeta2Tg mice at 4-16 weeks of age. Heart-to-body weight ratios of transgenic mice increased at 8 and 12 weeks, indicating hypertrophy, and ratios did not differ at 16 weeks. Collagen VI and fibronectin mRNA expression increased in PKCbeta2Tg hearts at 4-12 weeks. Histological examination revealed myocyte hypertrophy and fibrosis in 4- to 16-week PKCbeta2Tg hearts. CTGF expression increased in PKCbeta2Tg hearts at all ages, whereas TGFbeta increased only at 8 and 12 weeks. In 8-week diabetic mouse heart, CTGF and TGFbeta expression increased two- and fourfold, respectively. Similarly, CTGF expression increased in rat hearts at 2-8 weeks of diabetes. This is the first report of increased CTGF expression in myocardium of diabetic rodents suggesting that cardiac injury associated with PKCbeta2 activation, diabetes, or heart failure is marked by increased CTGF expression. CTGF could act independently or together with other cytokines to induce cardiac fibrosis and dysfunction.
Diabetes 2002 Sep
PMID:Expression of connective tissue growth factor is increased in injured myocardium associated with protein kinase C beta2 activation and diabetes. 1219 63

Collagen-mediated platelet activation contributes significantly to coronary and cerebrovascular thrombus formation associated with atherosclerotic plaque destabilization. Recent clinical and laboratory observations support a potential role for the platelet Fc receptor (FcgammaRIIA) in this process. The purpose of this study was to elucidate any association between platelet Fc receptor (FcR) expression levels and both atherosclerosis risk factors (ARFs) along with collagen-dependent platelet activation. Age and gender-independent variation has been described in the expression of this receptor that is stable over time. Platelet Fc surface expression was compared between patients experiencing an acute coronary or cerebrovascular event, healthy patients with two or more ARFs, and healthy patients with fewer than two ARFs. Platelet FcR expression was significantly and stably (6-52 weeks, mean 20 weeks) increased in 101 patients with acute myocardial infarction, unstable angina, or ischemic stroke syndrome (P<0.001) and 38 healthy patients with two or more ARFs (P=0.027) compared with 109 healthy patients with fewer than two ARFs. Patients with diabetes mellitus from all groups had significantly increased platelet FcR expression over those without diabetes (P<0.0001). Platelet aggregation studies suggested a correlation between number of ARFs per patient, platelet Fc expression levels, and relative sensitivity to collagen stimulation. Platelet FcR surface expression is increased in patients with an acute coronary or cerebrovascular event, non-acutely ill patients with two or more ARFs, and in patients with diabetes mellitus. Increased platelet FcR expression may therefore contribute towards risk for atherothrombotic events.
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PMID:Potential role of platelet FcgammaRIIA in collagen-mediated platelet activation associated with atherothrombosis. 1220 96


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