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)

As aminoguanidine (AG) is known to prevent non-enzymatic glycosylation in various tissues, we have histologically and biochemically evaluated AG effects on the skin in control, SZ-diabetic and AG-treated (25 mg/kgbw/day, 10w) diabetic rats. HbA1c and plasma glucose levels in diabetic and AG-treated diabetic rats were maintained about two times higher than those in control rats during the 10 weeks of the experiment. Histological findings revealed that the dermis in diabetic rats was thin and edematous, associated with swelling and degeneration of collagen fibers. Necrobiotic changes were seen in the lower dermis. These changes were greatly improved in AG-treated diabetic rats. Skin glucose contents in diabetic and AG-treated diabetic rats were about 10 times higher than those in the controls, whereas there was no difference in the sorbitol contents between three groups. Dry weight of the skin and collagen content was well correlated (r = 0.9044) and collagen represented 78.0 +/- 2.3% of the dry weight. By SDS-PAGE analysis of cyanogen bromide digests it was shown that high molecular weight peptides were increased in diabetic rats, but were decreased in AG-treated diabetic rats. The mean of glycosaminoglycan (GAG) contents of diabetic skin was 54% of that in the controls (1.58 +/- 0.09 vs. 2.94 +/- 0.39 micrograms/mg dry weight, P < 0.0025), which increased significantly in AG-treated diabetic rats (1.75 +/- 0.07 microgram/mg dry weight, P < 0.01 vs. diabetic).(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Res 1992
PMID:Amelioration of dermal lesions in streptozotocin-induced diabetic rats by aminoguanidine. 134 7

Tocopherol has been shown to have antiplatelet effects in insulin-dependent diabetes mellitus. However, its antiplatelet effect in non-insulin-dependent diabetes mellitus (NIDDM) remains to be established. In this report, the antiplatelet effect of tocopherol was assessed in a randomized, double-blind and crossover study of 15 NIDDM subjects. Each subject received tocopherol (dl-alpha-tocopherol nicotinate, 200 mg, tid) and a placebo for two six-week treatment periods separated by a three-week period in between for wash-out. The mechanisms of the antiplatelet effect of tocopherol were also studied in vitro. A significant decrease in platelet reactivity was observed after tocopherol treatment as compared with the pretest, and the magnitude of the decrease during tocopherol treatment was significantly evident when compared with that of the placebo treatment, as assessed by collagen (5, 10 micrograms/mL)-induced platelet aggregation of whole blood. A dose-dependent reduction in both ADP-and collagen-induced platelet aggregation was observed with tocopherol from 0.1 to 3.0 mM in vitro. No corresponding changes in ATP secretion and thromboxane synthesis were observed. Tocopherol also significantly inhibited fibrinogen-induced aggregation of elastase-treated platelets at a concentration of 0.1 mM. We demonstrated that platelet aggregation of whole blood ex vivo, among 15 NIDDM subjects was suppressed in tocopherol treatment, so tocopherol may have an antiplatelet effect in NIDDM subjects. The inhibitory effect of the platelet aggregation of tocopherol may be partially accomplished through interference with fibrinogen binding towards its receptor.
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PMID:Effect of tocopherol on platelet aggregation in non-insulin-dependent diabetes mellitus: ex vivo and in vitro studies. 135 87

We performed ultrastructural studies of skin lesions in seven adults with acquired perforating dermatosis. Three of the patients had diabetes mellitus and two were undergoing hemodialysis. Lesions in an early stage showed exocytosis of inflammatory cells and alteration of elastic fibers. Lesions in an intermediate stage featured discontinuities of the basement membrane and aggregates of electron-dense material lateral to the perforated focus, together with dermal edema, scattered macrophages, and densely aggregated collagen fibers that focally filled the papillary dermis. Later-stage lesions showed fibroblasts in the dermis and degenerated elastic fibers within transepidermal channels. In most cases there was a single large epidermal channel lined by flattened epithelial cells, and containing a variety of cellular and extracellular materials. Small "secondary" channels without abnormal keratinization were also observed within the epidermis. The findings suggest that altered keratinization is limited to the immediate vicinity of well-formed transepidermal channels, and that exocytosis of inflammatory cells and alterations of elastica are early and possibly key changes in lesion development. The unexpected discovery of hair fragments in one case suggests that curled hairs may play a role in the pathogenesis of some cases of acquired perforating dermatosis.
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PMID:Ultrastructural changes in acquired perforating dermatosis. 137 7

High ascorbic acid (AA) levels in the aqueous humor and intraocular tissues, including the lens, are thought to protect against the harmful effects of photochemical and ambient oxidation reactions involving oxygen and its radicals. In addition, AA may have various metabolic functions, including structural collagen formation in intraocular tissues. Recent work showed that, in the guinea pig, reduced AA was concentrated in the aqueous and lens epithelium. These in vivo studies were extended to streptozotocin-induced diabetic rats and guinea pigs to explore the state of AA transport and passive L-glucose movement in the diabetic lens. A bolus dose of radiolabeled test molecules, including 14C-AA, 3H-L-glucose (L-glu), and 14C-3-O-methyl-D-glucose, was injected into the blood at time zero, and the time-dependent concentrations of these labeled molecules were determined as they move into the aqueous humor, lens epithelium and capsule, and interior compartments. These kinetic studies provided a unique measurement of the functioning state of passive and carrier transport mechanisms in situ in normal and diabetic animals. Diabetic animals (blood glucose, greater than 300 mg/dl) were categorized in terms of the length of time of uniform monitored drug-induced diabetes as short term (10-20 days); midterm (40-60 days), and long term (100+ days). In the rat lens epithelium, significant decrease occurred in the active movement of AA (control KEi, 0.693 +/- 0.062 [n = 12]; midterm drug-induced diabetes Ki, 0.192 +/- 0.054 [n = 10]; t-test P less than 0.001). The passive L-glu entry rate increased (control KEi, 0.0268 +/- 0.0053 [n = 12]; midterm drug-induced diabetes KEi, 0.0421 +/- 0.075 [n = 10]; t-test P less than 0.005). Thus, it was suggested that the drug-induced diabetic rat lens epithelium had lost some of its ability to concentrate AA to high levels and achieved epithelial levels only one- to twofold those of aqueous; control animals concentrated AA to levels of five- to eightfold those of aqueous within 20 min. By contrast, the rate of movement of L-glu from epithelium to stroma increased minimally (control KSi, 0.0116 +/- 0.021 [n = 12]; midterm drug-induced diabetes KSi, 0.0136 +/- 0.034 [n = 10]; t-test P less than 0.05). In addition, AA entry rate into lens cortex increased fourfold (control KSi, = 0.0018 +/- 0.0003 [n = 12]; midterm drug-induced diabetes KSi, 0.0081 +/- 0.024 [n = 10]; t-test P less than 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Alterations in ascorbic acid transport into the lens of streptozotocin-induced diabetic rats and guinea pigs. 138 45

Pentosidine is an advanced glycosylation end product and protein cross-link that results from the reaction of pentoses with proteins. Recent data indicate that long-term glycation of proteins with glucose also leads to pentosidine formation through sugar fragmentation. In this study, the relationship between the severity of diabetic complications and pentosidine formation was investigated in collagen from skin-punch biopsies from 25 nondiabetic control subjects and 41 IDDM patients with diabetes duration greater than 17 yr. Pentosidine was significantly elevated in all IDDM patients versus control subjects (P less than 0.0001). It correlated strongly with age (P less than 0.0001) and weakly with duration (P less than 0.082). Age-adjusted pentosidine levels were highest in grade 2 (severe) versus grade 1 and 0 complication in all four parameters tested (retinopathy, proteinuria, arterial stiffness, and joint stiffness). Significant differences were found for retinopathy (P less than 0.014) and joint stiffness (P less than 0.041). The highest degree of association was with the cumulative grade of individual complication (P less than 0.005), determined by summing indexes of all four parameters. Pentosidine also was significantly elevated in the serum of IDDM patients compared with control subjects (P less than 0.0001), but levels were not significantly correlated with age, diabetes duration, complication, or skin collagen pentosidine (P greater than 0.05). A high correlation between pentosidine levels and long-wave collagen-linked fluorescence also was observed, suggesting that pentosidine is a generalized marker of accelerated tissue modification by the advanced glycosylation/Maillard reaction, which is enhanced in IDDM patients with severe complications.
Diabetes 1992 Oct
PMID:Pentosidine formation in skin correlates with severity of complications in individuals with long-standing IDDM. 139 2

Vitreous changes in diabetes can exacerbate proliferative diabetic retinopathy. These changes may be due to the effects of diabetes on vitreous collagen. Vitreous samples from 19 patients with proliferative diabetic retinopathy and 23 patients without diabetes were analyzed for collagen crosslinks, as well as for the early glycation products, glucitolyllysine and glucitolylhydroxylysine. Fluorometry was performed to measure advanced glycation end products. Vitreous collagen derived from diabetic patients was found to have significantly higher levels of the crosslink dihydroxylysinonorleucine (3.15 vs 1.24 mol/mol collagen, P<.01) than that of control subjects. Early glycation products were elevated in diabetic vitreous (1.65 vs 0.54 mol/mol collagen, P<.05). Levels of advanced glycation end products were 20 times higher in diabetic vitreous compared with the vitreous of controls. These diabetes-induced alterations of human vitreous may be of particular importance given the role of vitreous in proliferative diabetic retinopathy and vision loss.
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PMID:Biochemical abnormalities in vitreous of humans with proliferative diabetic retinopathy. 141 49

The existence of specific, age-related changes in gastrointestinal motility with clinical significance is controversial. Beside the more infrequent primary motility disorders, secondary motility disturbances associated with collagen vascular diseases, endocrinopathies, and neuromuscular diseases are prominent in the older and often multimorbid patients. Especially in geriatric patients, motility associated symptoms are undesired side-effects of drug therapy. The pathophysiology, clinical syndromes, and therapeutic principles of motility disorders in the elderly are discussed. The major symptoms of esophageal dysfunction are dysphagia, chest pain, heartburn, and regurgitation. Oropharyngeal dysphagia, mostly caused by cerebrovascular accidents and other neurologic disorders, leads to disturbances in food intake, and is often complicated by broncho-pulmonary infections arising from recurrent aspiration of food or saliva. Gastrointestinal reflux disease and spastic motility disorders of the esophagus are regarded as possible causes of angina-like chest pain after exclusion of cardiac diseases. Motility disturbances of the stomach and small bowel are often related to systemic disease (i.e., diabetes mellitus, chronic intestinal pseudo-obstruction) of drug side-effects. Mental and physical decline, reduced fluid intake, and constipating drugs are the most relevant factors for idiopathic constipation in the elderly. Fecal incontinence means a great psychological strain for older patients and leads to social isolation.
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PMID:[Gastrointestinal motility in the elderly]. 144 9

Platelets could contribute to vascular disease in diabetes through enhanced adherence to collagen exposed in injured vessels. Increased platelet adherence to collagen in diabetes could result from an alteration in platelets and/or platelet hypersensitivity to collagen that has been glycated to a greater extent. In this study, the adherence of platelets from diabetic or control subjects to glycated or nonglycated collagen coated onto glass surfaces was examined. Membrane fluidity of platelets was also determined, since decreased membrane fluidity associated with increased glycation of membrane proteins of platelets from diabetic subjects was shown in a previous study, and decreases in membrane fluidity have been shown by others to increase platelet adhesion. Thirteen diabetic subjects were compared with 13 age-and sex-matched control subjects. Collagen was glycated (9.7 nmol glucose/mg protein) by preincubation for 12 days in glucose-rich medium (500 mmol/L). A control solution of collagen incubated without glucose for the same time had 3.3 nmol glucose/mg protein. There were no differences in the adherence of platelets from diabetic and control subjects to nonglycated and glycated collagen-coated glass. The mean steady-state fluorescence polarization value (0.187 +/- 0.002) in 1.6-diphenyl-1,3,5-hexatriene-labeled platelets from diabetic subjects was significantly greater than in platelets from control subjects (0.174 +/- 0.002, p < 0.002); thus membrane fluidity in platelets from the group of diabetic subjects was decreased. The extent of glycation of membrane proteins from diabetic subjects (25.4 +/- 0.5 nmol glucose/mg protein) was significantly greater than from control subjects (20.2 +/- 0.4 nmol glucose/mg protein, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduced membrane fluidity and increased glycation of membrane proteins of platelets from diabetic subjects are not associated with increased platelet adherence to glycated collagen. 145 13

Streptozotocin-induced, insulin-deficient diabetic adult rats were daily administrated either minocycline or a chemically-modified non-antimicrobial tetracycline (CMT) by oral gavage for a 3-week time period; untreated diabetic and non-diabetic rats served as controls. On day 21, all rats received an intravenous injection of 3H-proline followed by perfusion fixation with an aldehyde mixture at 20 minutes and 4 hours after isotope injection. The upper and lower mandibles of these rats were dissected and processed for quantitative electron microscopic autoradiography to study 3H-proline utilization by fibroblasts in the periodontal ligament (PDL) of molars. In the non-diabetic controls, at 20 min after 3H-proline injection, radioprecursor was incorporated by the Golgi-RER system of PDL fibroblasts. At the 4-h time period, most of the label was present over the collagen fibers around these cells. In contrast, PDL fibroblasts in the untreated diabetic rats showed marked abnormalities ultrastructurally and minimal uptake (20 min) and secretion (4 h) of labeled proline. At both time periods, in both minocycline- and CMT-treated diabetic rats, fibroblasts were structurally more normal and the radioprecursor was localized in the fibroblasts and the PDL matrix in a pattern similar to that seen in the control rats. These results suggest that the diabetes-induced structural abnormalities and suppression of synthesis and secretion of protein (presumably collagen and its precursor) by PDL fibroblasts can be restored to near-normal by administration of a tetracycline and that this effect is mediated by a non-antimicrobial property of this family of antibiotics.
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PMID:Tetracycline administration increases protein (presumably procollagen) synthesis and secretion in periodontal ligament fibroblasts of streptozotocin-induced diabetic rats. 146 May 49

Glucose irreversibly modifies long-lived macromolecules by forming AGEs as a function of glucose concentration and time. AGEs cause qualitative and quantitative changes in extracellular matrix components such as type IV collagen, laminin, and vitronectin. These AGE-induced changes can affect cell adhesion, growth, and matrix accumulation. AGE-modified proteins also alter cell function by interacting with specific receptors on macrophages and endothelial cells, inducing changes that promote matrix overproduction, focal thrombosis, and vasoconstriction. DNA and nuclear proteins also may be targets for AGE damage. The persistence of accumulated AGEs during periods of normal glucose homeostasis may explain the phenomenon of hyperglycemic memory. Pharmacological inhibition of in vivo AGE formation by aminoguanidine prevents or ameliorates diabetic retinopathy, nephropathy, and neuropathy in animal models. These data suggest that aminoguanidine and other AGE inhibitors have a potential therapeutic role in the treatment of diabetic patients.
Diabetes Care 1992 Dec
PMID:Glycation products and the pathogenesis of diabetic complications. 146 41


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