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

The relationship between platelet abnormalities and vessel wall changes in diabetes is not known. We have examined the time course of alterations in in vitro platelet function and endothelial damage, as assessed by measurement of plasma levels of von Willebrand factor (VIIIR:WF) and factor VIII-related antigen (VIIIR:Ag), in streptozotocin-induced diabetic rats. Platelet aggregation and the platelet release reaction in response to ADP, thrombin, and collagen were measured in suspensions of washed platelets prepared from rats 3, 7, 14, or 28 days after induction of diabetes and in control animals. Platelets from diabetic animals showed enhanced aggregation response to ADP as early as 3 days after induction of diabetes and became hyperresponsive to thrombin after 7 days, compared to control platelets. Thrombin-induced release of serotonin was greater in platelets from diabetic animals at 14 days. Collagen-induced responses were not different at any time studied. VIIIR:WF was determined by ristocetin-induced platelet agglutination time in gel-filtered platelets, and VIIIR:Ag was determined by immunoelectrophoretic technique. VIIIR:WF and VIIIR:Ag were significantly enhanced in plasma from rats at 28 days after induction of diabetes and VIIIR:Ag was enhanced in plasma from rats at 14 days after induction of diabetes, but at the earlier times studied, neither were different from values in plasma from control-treated rats. Changes in VIIIR:WF and VIIIR:Ag therefore occurred later than the changes in platelet function. Plasma cholesterol concentrations were not significantly different at any of the times studied, but plasma triglyceride concentrations were significantly increased at 3 days and remained increased with further durations of diabetes. This may have contributed to the observed platelet and vessel wall changes. If these in vitro alterations reflect in vivo behavior, then platelet alterations occur before vessel wall changes and therefore do not appear to be a consequence of such changes in experimental diabetes mellitus.
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PMID:Time course of changes in in vitro platelet function and plasma von willebrand factor activity (VIIIR:WF) and factor VIII-related antigen (VIIIR:Ag) in the diabetic rat. 641 93

Aging and diabetes mellitus are associated with cross-linking and nonenzymatic glycosylation of collagen. Incubation of tendon fibers with reducing sugars results in increased breaking time in urea similar to that seen in aging, and in nonenzymatic glycosylation and browning. Effect of a sugar is proportional to the amount of sugar available in the open chain form. The increase in breaking time correlates with the appearance of chromophores characteristic of crosslinked browning products. Collagen altered by nonenzymatic browning may play a role in some age-like major complications of diabetes.
Diabetes 1984 Jan
PMID:Collagen aging in vitro by nonenzymatic glycosylation and browning. 641 98

Collagen metabolism was studied in 120 male patients with diabetes mellitus of different standing and severity. Collagen metabolism was assessed on the basis of free and peptide-bound blood hydroxyproline (FH and PBH). Collagen distruction prevailed over its biosynthesis in development and progress of diabetic microangiopathies, that resulted in the increased FH/PBH coefficient. Prolonged multimodality therapy of diabetes vascular complications led to a decrease in the FH level and simultaneous growth of PBH concentrations in the blood. The FH/PBH coefficient is an informative test for monitoring the vascular status in diabetes mellitus; this coefficient may be an indicator of the efficacy of treatment of diabetic microangiopathies.
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PMID:[Free and bound hydroxyproline in patients with diabetes mellitus]. 651 79

Collagen from human skin was fractionated into neutral salt-soluble, acid-soluble, pepsin-released, and insoluble fractions. No age-related changes were observed in the proportion of collagen extracted by neutral salt. A significant age-related decrease in the proportion of acid-soluble collagen was found. A highly significant (P less than 0.001) age-related decrease in the amount of collagen released by pepsin digestion was observed, with a concomitant age-related increase in the fraction of insoluble collagen. The amount of ketoamine-linked glucose bound to this insoluble collagen also increased significantly with age. Skin collagen from three juvenile onset diabetics (JOD) and one young maturity onset diabetic (MOD) appeared to have undergone accelerated aging. JOD and the young MOD had significantly less collagen released by pepsin digestion and significantly more insoluble collagen than would be predicted by their ages. The collagen released by pepsin digestion of the diabetic samples had more high molecular weight components than similar fractions obtained from age-matched nondiabetic controls. There was also more ketoamine-linked glucose bound to the insoluble collagen of JOD than to that fraction from comparably aged control subjects. The apparent acceleration of collagen aging in diabetes mellitus may play a role in complications of diabetes that occur in collagen-rich tissues.
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PMID:Effects of age and diabetes mellitus on the solubility and nonenzymatic glucosylation of human skin collagen. 678 79

This study was undertaken in an animal model of mild diabetes to determine if provision of chronic insulin replacement during postprandial hyperglycemia may modify the abnormalities of myocardium. Group 1 served as controls with normal glucose tolerance by intravenous testing. Two additional groups were made diabetic with low doses of alloxan. Diabetic animals of Group 2 were untreated (n = 6). Group 3 animals (n = 6) received regular insulin daily to reduce postprandial hyperglycemia. After one year with maintained body weight, the animals were studied in the intact anesthetized state using the indicator dilution technique for left ventricular volume determinations. Basal left ventricular function and contractility were similar to normals in both diabetic groups. During intraventricular infusion of saline, end-diastolic pressure rose to higher levels in untreated diabetes (14.8 +/- 2 mm Hg) than normals (8.8 +/- 0.84), despite similar basal levels. Insulin treatment was associated with higher filling pressures than in group 1 as well as reduced end-diastolic volume response. Collagen concentrations were enhanced an average of 50% in layers from the inner to outer myocardium in both untreated and treated diabetics, associated with sodium and water accumulation. Since hypertrophy was not present, the diminished compliance appeared related to increased collagen levels. On electron microscopy, the subcellular organelles of the cardiac cell appeared normal in both diabetic groups. Thus, collagen accumulation and abnormal myocardial function in this model of diabetes is not affected by control of postprandial hyperglycemia, but a potential role for sustained hormone replacement is not excluded.
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PMID:Myocardial composition and function in diabetes. The effects of chronic insulin use. 703 May 14

In 1972, Wolcott and Rallison described three siblings with a combination of infancy-onset diabetes mellitus and multiple epiphyseal dysplasia. We have observed a brother and sister with the same disorder. The chondro-osseous lesions are those of a spondylo-epiphyseal dysplasia. The diabetes mellitus is relatively mild. Histologic and electron microscopic studies of chondro-osseous tissue show findings similar to those in other epiphyseal and spondylo-epiphyseal dysplasias. In addition, however, atypical collagen-like fibres are found inside and outside chondrocytes. Collagen production seems to be normal in cultured fibroblasts. From the available data it appears that the association of characteristic chondro-osseous and endocrine abnormalities is non-random and that the lesions are independent manifestations of a pleiotropic gene. We propose to call this disorder the Wolcott-Rallison Syndrome.
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PMID:Wolcott-Rallison syndrome: diabetes mellitus and spondyloepiphyseal dysplasia. 709 31

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

The effect of diabetes on myocardial collagen metabolism was investigated in rats. Diabetes was induced by an i.v. injection of streptozotocin (60 mg/kg). The animals were killed after 3, 6, 18, or 26 wk of diabetes. Urinary glucose levels were measured by Tes-Tape. The myocardium was quickly removed and homogenized. Collagen was estimated by hydroxyproline content. Collagen synthesis was measured by 14C-proline incorporation. Myocardial collagen concentration and collagen synthesis was not altered in the diabetic rats. Collagen concentration did appear to increase in the 18- and 26-wk rats, but this was probably an age-related phenomenon. These results suggest that diabetes does not alter collagen metabolism in rats.
Diabetes 1980 Jul
PMID:Collagen metabolism in the myocardium from streptozotocin-diabetic rats. 738 Jan 16

The relationship between the extractability of collagen by enzymatic digestion and the degree of nonenzymatic glycation of collagen was examined in the aorta and skin from 38 subjects without diabetes mellitus (mean age: 62.3 +/- 20.2 years). Samples were obtained from the aortic media (M), lesion-free intima (I), atherosclerotic intima (A) and dermis of the skin (S). Collagen was extracted first by incubation with 1/50 (enzyme/substrate weight ratio) pepsin at 4 degrees C for 24 h (P-fraction) and then by incubation with 1/10 (enzyme/substrate weight ratio) pepsin at room temperature for 24 h (EP-fraction). The pepsin-insoluble precipitates were digested by incubation with 270 units of bacterial collagenase at 37 degrees C for 24 h (PIS-fraction). Collagen contents, ketoamines and collagen-linked fluorescence (CLF) were measured in each fraction. The amount of ketoamines and the level of CLF correlated inversely with the susceptibility of collagen to pepsin digestion in various tissues, including M, I, A and S. These values were highest in both the P- and EP-fractions of M, which contained the least amount of collagen extracted by pepsin digestion. In contrast, they were lowest in S, where the concentration of collagen extracted by pepsin digestion was greatest among all of the tissue samples. Atherosclerotic intima (A) and aortic media (M) showed an age-related increase in the total amount of collagen digested with pepsin and collagenase, which depended mainly on an increase in the content of pepsin-insoluble collagen. Although the total amount of collagen did not increase with advancing age in I or S, collagen in I and S became progressingly resistant to pepsin digestion. These results suggest that the age-related decrease in the susceptibility of collagen to pepsin digestion may be due to nonenzymatic glycation in atherosclerotic lesions as well as normal tissues, including the aortic media, lesion-free intima and skin. The level of CLF significantly increased with age in the P-fraction and/or EP fraction of M, I and S. However, there was no relationship between the level of CLF and the subject's age in A. Thus, the accumulation of advanced glycation endproducts (AGEs) on collagen fibers may be partially responsible for the increase in collagen matrix in atherosclerotic lesions of subjects without diabetes mellitus.
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PMID:Nonenzymatic glycation and extractability of collagen in human atherosclerotic plaques. 748 34

L-fucose is a monosaccharide which is present in low concentrations in normal serum but is increased in diabetes, cancer, and inflammatory diseases. The contribution that abnormal L-fucose levels make to the progression of these disorders is unknown. In a previous study we showed that increased L-fucose concentration reduced proliferation and proteoglycan production by cultured cerebral microvessel endothelial cells. In the present study we show that exposing cerebral microvessel endothelial cells for 2 weeks to medium containing an increased concentration of L-fucose causes a significant decrease in collagen and to a lesser extent noncollagen protein production. The effect of L-fucose on collagen and noncollagen protein production is concentration-dependent: 1 mM L-fucose causes a significant decrease in collagen production but has no effect on noncollagen protein production; a 5 mM L-fucose concentration causes a maximum decrease in both collagen and noncollagen protein production. This defect is unrelated to the reduction in myo-inositol uptake caused by L-fucose and is not prevented by aminoguanidine. Collagen production can be improved by restoring L-fucose-conditioned cells to normal medium. Culturing cells for 2 weeks in medium containing 10 mM L-fucose resulted in a 50% decrease in collagen production, which was restored to 75% of control after cells were transferred to normal medium for 7 days. In contrast, noncollagen protein production was totally restored after 3 days in normal medium. Increasing levels of L-fucose in serum of rats also resulted in a decrease in collagen production. Collagenase digestible incorporation of L-[2,3,4,5-3H]proline into protein of the articular cartilage from rats fed a diet containing 20% L-fucose for 3 weeks was reduced by about 40% compared to rats fed a normal diet. The decrease in collagen production in L-fucose fed rats was less than the reduction that occurred in streptozotocin-induced diabetic rats. These data suggest that changes in L-fucose concentration itself may be a factor in the regulation of collagen production.
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PMID:L-fucose reduces collagen and noncollagen protein production in cultured cerebral microvessel endothelial cells. 759 46


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