Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of glucose and ascorbic acid on in vitro collagen and DNA synthesis were evaluated in human umbilical vein endothelial cells. Ascorbic acid significantly potentiated collagen synthesis. Incubation of cells with elevated glucose concentration for 24h significantly reduced [3H]-thymidine uptake (2h). However, the addition of ascorbic acid (0.1 mM) dramatically prevented the inhibition of thymidine uptake. Based on these data, it is suggested that ascorbic acid supplementation in diabetics may prevent or ameliorate diabetic angiopathy.
Diabetes Res 1991 Oct
PMID:Ascorbic acid prevents the inhibition of DNA synthesis induced by high glucose concentration in cultured human endothelial cells. 184 14

This study evaluated three hydroxyapatite (HA) preparations placed subperiosteally in rats given streptozotocin (70 mg/kg) to induce diabetes (ID) (n = 24) and in nondiabetic (ND) rats (n = 24) used as controls. Implants of 1) nonporous HA granules (HAG), 2) HA granules hand-mixed with bovine collagen (HACM), and 3) HA granules and purified fibrillar collagen in a preprocessed block (PFC-HA) were randomly placed in subperiosteal pockets created on the cranium and adjacent to the left/right mandibles of each rat. Six rats from each group were killed at 3, 6, 12, and 24 weeks postimplantation. Animals killed after 3 weeks showed sporadic bone proliferation and bone resorption, whereas those killed after 6, 12, and 24 weeks showed formation of new bone at the implant/bone interface. Contact of the implant with bone was a requirement for osteogenesis, but bone formed only into the basilar layers of the implants. The ID group showed the greatest inflammatory response as well as the greatest degree of osteogenesis at all intervals of time. The addition of collagen to HA appeared to reduce the inflammatory response. Specimens implanted with HACM showed the least inflammation of the three implanted materials in both ID and ND groups.
 ...
PMID:Extracranial and mandibular augmentation with hydroxyapatite-collagen in induced diabetic and nondiabetic rats. 184 50

The Maillard or browning reaction between reducing sugars and protein contributes to the chemical deterioration and loss of nutritional value of proteins during food processing and storage. This article presents and discusses evidence that the Maillard reaction is also involved in the chemical aging of long-lived proteins in human tissues. While the concentration of the Amadori adduct of glucose to lens protein and skin collagen is relatively constant with age, products of sequential glycation and oxidation of protein, termed glycoxidation products, accumulate in these long-lived proteins with advancing age and at an accelerated rate in diabetes. Among these products are the chemically modified amino acids, N epsilon-(carboxymethyl)lysine (CML), N epsilon-(carboxymethyl)hydroxylysine (CMhL), and the fluorescent crosslink, pentosidine. While these glycoxidation products are present at only trace levels in tissue proteins, there is strong evidence for the presence of other browning products which remain to be characterized. Mechanisms for detoxifying reactive intermediates in the Maillard reaction and catabolism of extensively browned proteins are also discussed, along with recent approaches for therapeutic modulation of advanced stages of the Maillard reaction.
 ...
PMID:The Maillard reaction in vivo. 185 26

The effect of aminoguanidine (AG) on diabetic proteinuria was studied in control rats ([C]), streptozotocin (SZ)-induced diabetic rats ([DM]), control rats treated with AG [( C + AG]), or diabetic rats treated with AG [( DM + AG]). Increased glycation of hemoglobin (HbA1C), and glomerular basement membrane (GBM) type IV collagen (IV-C) at 10 wk of stable diabetes were associated with the appearance of high-molecular-weight (HMW) cross-linked type I collagen and HMW proteinuria of 62 kD, 69 kD albumin and 77 kD proteins to the levels of 362, 381, and 408%, while 9.9, 13.5, 17, 18, and 23 kD proteins were decreased, respectively, to non-detectable, 37, 16, and 13%. AG decreased cross-linkage of type I collagen and significantly decreased urinary 62 kD protein to 54%, 69 kD albumin to 40%, and 77 kD protein to 49% at 10 wk in [DM + AG] compared to [DM] without changing diabetic control. It is suggested that glycation-derived late-stage protein modification is etiologically important for diabetic proteinuria, and that AG can potentially prevent diabetic HMW proteinuria.
 ...
PMID:Aminoguanidine decreases urinary albumin and high-molecular-weight proteins in diabetic rats. 187 97

Results show that diabetes, which is a major risk factor for arterio-atherosclerosis, mimicks an accelerated aging, at least as far as the thickening of basement membranes and fibronectin and collagen biosynthesis are concerned. A similar sequence of events could be demonstrated in human atherosclerotic plaque formation. In conclusion, we could demonstrate a disregulation of extracellular matrix components biosynthesis (type-III collagen and fibronectin) in diabetes and atherosclerosis.
 ...
PMID:Modifications of the biosynthesis of type-I and type-III collagens and fibronectin during diabetes and atherosclerosis. 187 89

Abnormalities of ascorbic acid metabolism have been reported in experimentally-induced diabetes and in diabetic patients. Ascorbate is a powerful antioxidant, a cofactor in collagen biosynthesis, and affects platelet activation, prostaglandin synthesis and the polyol pathway. This suggests a possible close interrelationship between ascorbic acid metabolism and pathways known to be influenced by diabetes. We determined serum ascorbic acid and its metabolite, dehydroascorbic acid, as indices of antioxidant status, and the ratio, dehydroascorbate/ascorbate, as an index of oxidative stress, in 20 matched diabetic patients with and 20 without microangiopathy and in 22 age-matched control subjects. Each study subject then took ascorbic acid, 1 g daily orally, for six weeks with repeat measurements taken at three and six weeks. At baseline, patients with microangiopathy had lower ascorbic acid concentrations than those without microangiopathy and control subjects (42.1 +/- 19.3 vs 55.6 +/- 20.0, p less than 0.01, vs 82.9 +/- 30.9 mumol/l, p less than 0.001) and elevated dehydroascorbate/ascorbate ratios (0.87 +/- 0.46 vs 0.61 +/- 0.26, p less than 0.01, vs 0.38 +/- 0.14, p less than 0.001). At three weeks, ascorbate concentrations rose in all groups (p less than 0.0001) and was maintained in control subjects (151.5 +/- 56.3 mumol/l), but fell in both diabetic groups by six weeks (p less than 0.01). Dehydroascorbate/ascorbate ratios fell in all groups at three weeks (p less than 0.0001) but rose again in the diabetic groups by six weeks (p less than 0.001) and was unchanged in the control subjects. Dehydroascorbate concentrations rose significantly from baseline in all groups by six weeks of ascorbic acid supplementation (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Disturbed handling of ascorbic acid in diabetic patients with and without microangiopathy during high dose ascorbate supplementation. 188 88

The intracellular concentration of calcium (Cai) was measured in platelets of healthy control subjects and diabetics type II. Cai was elevated in platelets of diabetics type II under basal conditions, after stimulation by collagen, in the presence and absence of calcium in the incubation medium. The increase in Cai after stimulation by collagen was inhibited by nitrendipine in both kinds of platelets, however Cai remained elevated in platelets of diabetics. Our data and findings of others may be understood as indications of disturbances in the handling of Cai in diabetes.
 ...
PMID:Increase in the cytosolic concentration of calcium in platelets of diabetics type II. 189 61

Incubation of corneal collagen type I with glucose in the presence of transition metal ions (copper, iron) results in the formation of collagen aggregates insoluble in 6 M urea, and in 2% sodium dodecyl sulfate + 5% beta-mercaptoethanol. The reaction is mediated by hydrogen peroxide and transition metals since it is inhibited by catalase and by the chelating agent diethylenetriaminepentaacetic acid. Comparative studies showed that copper is more efficient than iron and that the reaction proceeds more rapidly with ribose than with glucose. The data support a mechanism involving transition metal ion catalyzed autoxidation of glucose (and possibly of Amadori products) with generation of superoxide radical. Superoxide dismutation produces hydrogen peroxide, which then generates hydroxyl radicals in the presence of transition metal ions (Fenton reaction). Hydroxyl radical attack is known to lead to cross-linking, which is enhanced in glycated proteins. The experimental data presented are consistent with in vivo alteration of collagen properties during normal aging and with the acceleration of similar changes in diabetes mellitus.
 ...
PMID:The role of nonenzymatic glycosylation, transition metals, and free radicals in the formation of collagen aggregates. 189 43

Carboxymethyllysine (CML) has been identified as a modified amino acid that accumulates with age in human lens proteins and collagen. CML may be formed by oxidation of fructoselysine (FL), the Amadori adduct formed on nonenzymatic glycosylation of lysine residues in protein, or by reaction of ascorbate with protein under autoxidizing conditions. We proposed that measurements of tissue and urinary CML may be useful as indices of oxidative stress or damage to proteins in vivo. To determine the extent to which oxidation of nonenzymatically glycosylated proteins contributes to urinary CML, we measured the urinary concentrations of FL and CML in diabetic (n = 26) and control (n = 28) patients. The urinary concentration of FL correlated strongly with HbA1 measurements and was significantly higher in diabetic compared with control samples (9.2 +/- 6.5 and 4.0 +/- 2.8 micrograms/mg creatinine, respectively; P less than 0.0001). There was also a strong correlation between the concentrations of CML and FL in both diabetic and control urine (r = 0.67, P less than 0.0001) but only a weakly significant increase in the CML concentration in diabetic compared with control urine (1.2 +/- 0.5 and 1.0 +/- 0.3 micrograms/mg creatinine, respectively; P = 0.05). The molar ratio of CML to FL was significantly lower in diabetic compared with control patients (0.25 +/- 0.12 and 0.43 +/- 0.16, respectively; P less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1991 Feb
PMID:Effect of diabetes and aging on carboxymethyllysine levels in human urine. 189 6

Chronic experimental hyperglycemia mediated by galactose has been shown to induce browning and cross-linking of rat tail tendon collagen that could be duplicated in vitro by nonenzymatic galactosylation. To investigate the nature of these changes, Sprague-Dawley rats were placed on a 33% galactose diet without and with sorbinil for 6 and 12 mo. Collagen-linked fluorescence and pentosidine cross-links increased with age and galactosemia in tail tendons (P less than 0.001) and skin but were essentially unresponsive to aldose reductase inhibition (ARI). In contrast, tendon breaking time in urea, a likely parameter of cross-linking, was markedly improved (P less than 0.001) by ARI. Fluorescence that was inhibited by sorbinil treatment was increased in pepsin and proteinase K digest of aortic tissue from galactosemic rats (P less than 0.001), but impaired enzymatic digestibility was not observed. Systolic blood pressure as potential consequence of aortic stiffening was not increased in galactosemia. These data suggest that fluorescence in skin and tendon might be in part due to advanced glycosylation and pentosidine formation because these were not decreased by ARI. However, they also suggest that nonfluorescent cross-links may also be forming because, in contrast to fluorescence, tail tendon breaking time was partly corrected by ARI. Thus, it appears that extracellular matrix changes in chronic galactosemia are complex, being partly attributable to advanced glycosylation and partly to polyol-pathway activation.
Diabetes 1991 Aug
PMID:Tissue-specific effects of aldose reductase inhibition on fluorescence and cross-linking of extracellular matrix in chronic galactosemia. Relationship to pentosidine cross-links. 190 47


<< Previous 1 2 3 4 5 6 7 8 9 10