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

Collagen and proteoglycans are two major constituents of the extracellular matrix, and their abnormalities have been incriminated in the pathogenesis of diabetic complications. A decrease of plasma ascorbic acid has been reported in diabetes and thus may play a role in the collagen and proteoglycan abnormalities in diabetes. Ascorbic acid and glucose share structural similarity, and their metabolism may interact at the level of membrane transport and cellular action. In this study, we used a fibroblast culture system to explore this possibility. Ascorbic acid increased collagen and proteoglycan both in the culture medium and the cell layer. This stimulatory action of ascorbic acid was inhibited by the presence of glucose at a concentration of 25 mM. The effect of high glucose concentration was not mediated by inhibition of ascorbic acid uptake by fibroblasts. Insulin is able to abolish this inhibitory action of glucose on collagen production, but the precise mechanism is unclear. These results show that the high glucose concentration in diabetes can impair the action of ascorbic acid at the cellular level. This may further accentuate the problem of decreased availability of this vitamin as a result of its low plasma concentration.
Diabetes 1991 Mar
PMID:Interaction of ascorbic acid and glucose on production of collagen and proteoglycan by fibroblasts. 199 79

The determination of glycated haemoglobin permits a good evaluation of metabolic regulation of diabetics. The development of vascular complications depends on duration and degree of hyperglycemia. It is presented the different chemical reactions of glucose with proteins in diabetes. The consequences are structural and functional changes of a variety of human proteins. This is a part of long-term complications of diabetics. Collagen is used as an example for a protein with a relatively slow turnover rate that could allow for an accumulation of altered protein.
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PMID:[The significance of HbA1 determination in children]. 218 96

Streptozotocin (STZ)-induced diabetes depresses the rate of vascular collagen synthesis in the spontaneously hypertensive rat (SHR), but it also reduces arterial pressure (SAP) in this strain. We investigated this phenomenon further by comparing the SHR with the renovascular hypertensive (RVH) rat, because diabetes does not affect SAP in the latter model of hypertension. Renovascular hypertension was induced by clipping the left renal artery of Wistar-Kyoto (WKY) rats; sham-operated WKY were included as normotensive controls. Collagen synthesis of arterial tissue in vitro was quantified as prolyl hydroxylase activity and the rate of radioactive proline incorporation into collagen. Arterial collagen synthesis of nondiabetic SHR and RVH animals was elevated compared to that of the nonhypertensive WKY controls. STZ-induced diabetes (8 weeks) reduced SAP of SHR, but had no effect on SAP of either RVH or normotensive WKY rats. However, diabetes significantly depressed vascular collagen synthesis of both SHR and RVH rats, and, less consistently, of the WKY. The results strongly suggest that STZ-induced diabetes in SHR impairs arterial collagen synthesis independent of associated changes in arterial pressure.
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PMID:STZ-induced diabetes in SHR and renovascular hypertensive rats: dissociation between changes in arterial pressure and vascular collagen synthesis. 224 11

Our objective was to determine whether the fluorescence of skin collagen, which may reflect the accumulation of advanced glycosylation end products, is increased in young patients with type I (insulin-dependent) diabetes. Our study design was a cross-sectional case-control study in a referral-based diabetic clinic in an academic hospital. Study subjects comprised a convenience sample of 18 type I diabetic patients aged 17-30 yr and 8 age-matched healthy control subjects. The fluorescence of collagen was measured in skin biopsy material. Collagen-linked fluorescence (CLF) was increased in diabetic patients (mean 10.5 [range 5.8-15.8] U/mg) compared with control subjects (7.6 [5.6-10.1] U/mg, P less than 0.02). In diabetic patients, CLF was related to age (r = 0.581) and duration of diabetes (r = 0.697) but not concentration of glycosylated hemoglobin (r = 0.082). Partial correlation analysis demonstrated that duration of diabetes is the main factor determining the fluorescence of collagen in these patients. There was a relationship between CLF and presence of diabetic retinopathy after the data were adjusted for patient age and duration of diabetes (P = 0.023). Increased fluorescence of skin collagen can be detected in young type I diabetic patients and is primarily related to duration of diabetes.
Diabetes Care 1990 May
PMID:Increased collagen-linked fluorescence in skin of young patients with type I diabetes mellitus. 235 Oct 24

Platelet aggregation in response to collagen, adenosine diphosphate and arachidonic acid was studied prospectively in 30 children with Type 1 (insulin-dependent) diabetes mellitus. The studies began on admission to hospital and continued throughout the two years following diagnosis. The results were compared with those in 44 health control children. Collagen-induced aggregation was significantly decreased in the diabetic children on admission in comparison to the healthy children. In contrast, the aggregation induced by adenosine diphosphate (1.1 mumols/l, p less than 0.05) and arachidonic acid (0.25 mmol/l, p less than 0.05) was increased on admission. The magnitude of the platelet shape change after adenosine diphosphate stimulation was small at the onset of the disease but was significantly increased towards normal during the two years of follow-up. On admission, the primary wave aggregation induced by adenosine diphosphate was positively and significantly correlated to some of the lipoprotein fractions that were disturbed at that time, especially triglycerides in high-density lipoproteins. After two years of treatment the platelet aggregability in the diabetic children had been restored to normal.
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PMID:Platelet aggregability during the first two years of type 1 (insulin-dependent) diabetes mellitus in children. 251 90

Various parameters were used in observing the process of wound healing in rats with streptozotocin-induced diabetes (STZ diabetes). Sections stained according to the Hematoxylin-Eosin, Van-Gieson, and Azan methods were used in observing histological changes. At the same time, wound strength during the healing was measured as a parameter for evaluating the healing process. In addition, changes in leukocytes, plasma fibrinogen, activated factor XIII (aXIII), collagen content of the incised wound, and metabolic changes were determined. Results 1. Histological studies showed that, in STZ diabetes, the inflammatory response was minimal and occurred later than in normal cases. In the incised wound, cellular infiltration of polymorpho-nuclear leukocytes and fibrin nets accumulated poorly. The fibrin net was coarse and fragile. Furthermore, epithelialization of the wound was late: it did not occur until 5 days after the operation. In cases of STZ diabetes, patterns of hyperplasia and fibroblast arrangements were abnormal. Collagen regeneration and proliferation processes were remarkably retarded. 2. In normal, wound strength increased from the 5 postoperative day. After 10 days had passed, it increased remarkably until, after 30 days, it had returned to the preoperative level. In STZ diabetes, however, no increase in wound strength occurred for the first 14 days after the operation. There after strength increased slowly; but, 40 days after the operation, 80% of the preoperative level still had not been reached. 3. Changes in leukocytes were much later occurring in STZ diabetes than in normal. Recovery took longer than in normal. 4. In STZ diabetes, increases in plasma fibrinogen and decreases of the aXIII factor were slower than in normal. The a XIII factor decreased remarkably, and recovery was slow. 5. In terms of collagen content in the wound incision, in STZ diabetes, tropocollagen increase occurred later than in normal. But, from the 5 to the 14 postoperative days, its level was higher than that in normal. Maturation-process collagen and mature collagen increased still more slowly. In normal, mature collagen had reached preoperative level 20 days after the operation, in STZ diabetes, 80% of preoperative level still had not been reached 30 days after the operation. 6. These studies showed that the following factors hinder wound healing in cases of diabetes mellitus: minimal inflammatory response, incomplete formation of the fibrin nets, retardation of epithelialization, retarded action of plasma fibrinogen and the a XIII factor, reduced fibroblast activity, and slow increase in collagen content.
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PMID:[Experimental studies of skin wound healing process by first intention in streptozotocin-induced diabetes mellitus rats]. 263 77

Although changes in collagen production probably play a major role in the connective tissue defects of diabetes, we do not know to what extent these changes are attributable to hormonal/metabolic versus nutritional alterations. To study collagen production as influenced separately by nutrition versus hormonal/metabolic factors, rats were given 50 mg/kg i.v. streptozocin (STZ) (mild weight-gaining diabetes) or 100 mg/kg STZ (severe weight-losing diabetes) and compared with nondiabetic food-restricted rats to match weight changes in diabetic animals. Articular cartilage was incubated with [3H]proline, and uptake of [3H]proline into both collagen and noncollagen proteins was determined with purified bacterial collagenase. Collagen decreased to 49% in mildly diabetic rats and 16% in severely diabetic rats, compared with control rats fed ad libitum and decreased to 85 and 73%, respectively, in food-restricted rats (both P less than .01 vs. diabetes). Diabetes induced a greater defect in collagen production than food restriction and a greater decrease in collagen than noncollagen protein production within each group, suggesting a specific effect on collagen. With comparable levels of metabolic severity (glucose, beta-hydroxybutyrate), diabetic animals that lost weight produced significantly less collagen than animals that gained weight, suggesting separate mechanisms. Quantitation of the impact of undernutrition on collagen production in diabetes demonstrated that approximately 31 to 32% of the defect was due to undernutrition, leaving approximately 68-69% of the defect due to the diabetic state.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1989 Jun
PMID:Nutritional and hormonal regulation of articular collagen production in diabetic animals. 272 23

Collagen undergoes progressive browning with aging and diabetes characterized by yellowing, fluorescence and crosslinking, the cause of which remains unelucidated. As an initial step towards understanding the mechanism(s) of insolubilization of collagen in aging, the major fluorophores/chromophores from the insoluble fraction of human dura mater were isolated and their spectroscopic properties were characterized. High molecular weight tryptic peptides of insoluble collagen were cleaved by sequential enzymatic digestion followed by separation into high (HMW) and low molecular weight (LMW) fractions by gel filtration chromatography. LMW was further separated by paper and reverse phase chromatography (HPLC). Two fluorescent peaks, nicknamed P and M, were obtained from LMW which had UV maxima at 325 and 350 nm and excitation/fluorescence maxima at 335/385 and 360/460 nm, respectively. Fluorophore M was borohydride reducible and unstable to acid-hydrolysis, while P remained unaffected. Large quantities of fluorophore M and pyridinoline were found in the highly crosslinked HMW fraction remaining following exhaustive proteolytic digestion. Fluorophore P and M were the major fluorophores recovered from the tryptic digest of insoluble dura mater. Fluorescence spectra of M suggest an iminopropene type of configuration which could result from nonenzymatic browning of collagen with, e.g., glucose or malonyldialdehyde, as a result of lipid peroxidation. Spectroscopic and chemical properties of fluorophore P were reminiscent but not identical with those of pyridinium crosslinks. Structure elucidation of these fluorophores is expected to provide important insight into the aging processes of the extracellular matrix.
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PMID:Isolation, purification and partial characterization of novel fluorophores from aging human insoluble collagen-rich tissue. 279 58

Collagen production and collagenase activity were measured in dermal fibroblast cultures obtained from eight patients with diabetes with digital sclerosis and three normal controls. Total collagen synthesis in patients with diabetes was reduced in comparison with controls. DNA replication was also reduced in patients with diabetes. No differences in collagenase activity were noted. Our results suggest that, in contrast to systemic sclerosis, increased synthesis does not contribute to the collagen accumulation of diabetic digital sclerosis. Decreased degradation related to nonenzymatic glucosylation of collagen is a more likely mechanism.
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PMID:Collagen synthesis and collagenase activity in dermal fibroblasts from patients with diabetes and digital sclerosis. 298 79

Several pathways are activated when platelets aggregate and undergo the release reaction. We have examined the relative importance of these pathways in the responses to adenosine diphosphate (ADP), thrombin, or collagen of washed platelets from rats with diabetes induced by streptozocin. ADP-induced aggregation was enhanced without the release reaction with platelets from diabetic rats. Collagen-induced aggregation and release, and the adherence of platelets to collagen-coated glass were similar with platelets from diabetic and control rats. Thrombin (1 U/ml) induced more extensive loss of tritium from 3H-arachidonic acid-labeled platelets from diabetic rats than from control rats. Platelet aggregation and the release of 14C-serotonin from prelabeled platelets was greater in response to low concentrations of thrombin (0.04 U/ml). Creatine phosphate-creatine phosphokinase (CP/CPK) and aspirin completely blocked aggregation and partially blocked the release of granule contents from platelets from control and diabetic rats exposed to this low concentration of thrombin. Thus, the enhanced platelet aggregation in response to low concentrations of thrombin was likely mediated in part by released ADP and products formed from arachidonate. In contrast, with a higher concentration of thrombin (0.0625 U/ml), CP/CPK and aspirin did not inhibit the increased sensitivity of diabetic platelets to thrombin-induced aggregation and release; the concentrations of CP/CPK completely blocked aggregation induced by ADP (10 mumol/L), and the aspirin inhibited thromboxane B2 production in response to thrombin (1 U/ml) by 99%. Thus, a thrombin-induced pathway(s) of aggregation and release independent of released ADP and the products of arachidonate metabolism is enhanced in platelets from diabetic rats.
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PMID:Pathways responsible for platelet hypersensitivity in rats with diabetes. I. Streptozocin-induced diabetes. 308 May 38


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