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)

Diabetes mellitus is associated with a high incidence of cardiovascular diseases not directly attributable to hyperlipidemia, smoking, or hypertension, but which in part may be explained by an enhanced tendency to thrombosis due to increased platelet activity. The aim of this study was to evaluate platelet function and compare the effectiveness of the antiplatelet drug aspirin on platelet aggregation in diabetic and nondiabetic subjects. Platelet aggregation and composition were examined in 20 male insulin-dependent diabetes mellitus (IDDM) patients and 20 nondiabetic control subjects matched for age and body mass index. All were normotensive with serum total cholesterol less than 6.5 mM. Although within the clinically acceptable normal range, blood pressure was significantly higher in diabetic patients (130/75 mmHg) than in control subjects (123/70 mmHg) (P less than 0.05). Serum thromboxane B2 and ex vivo aggregation of platelets in response to two doses of the agonists collagen and platelet-activating factor (PAF) were similar to nondiabetic subjects. However, after taking 100 mg/day aspirin for 5 days, platelet aggregation to collagen was reduced by 76% in control subjects compared to 56% in IDDM patients (P less than 0.001). Aspirin treatment also reduced the slope of the aggregation curve and increased the lag time (the period between the addition of collagen and the start of irreversible aggregation) significantly more in control than in diabetic platelets. This difference in platelet aggregation could not be attributed to differences in platelet serotonin or thromboxane A2 secretion, the latter being almost completely suppressed by aspirin in each group. Platelet aggregation to PAF was similar in both groups and was not affected by aspirin.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1992 Mar
PMID:Differential effect of aspirin on platelet aggregation in IDDM. 155 86

Changes of platelet aggregation in relation to macroangiopathy and to some of its risk factors were observed in microangiopathy-free, well-controlled type 1 diabetic males. Platelet aggregate ratio was generally lower in patients (n = 77) than in age-matched healthy subjects (n = 48). In the absence of cigarette smoking, hypertension, obesity and hypercholesterolemia (n = 25) in vitro platelet hyperaggregation was found induced with epinephrine, collagen or arachidonic acid, and to a lesser degree with ADP. There was no change in the presence of at least one risk factor in addition to diabetes (n = 29), but there was a further significant increase in platelet aggregation when overt coronary, cerebral or peripheral artery disease was present (n = 23).
Diabetes Res Clin Pract 1992 Feb
PMID:Platelet function in male diabetics with and without macrovascular complications. 156 30

In vitro studies have demonstrated that gliclazide has free radical scavenging and antiplatelet activities. To assess this clinically, we studied gliclazide in a blinded, randomized, glibenclamide-controlled trial in 30 type II diabetic patients with retinopathy. All patients had been taking glibenclamide for more than 12 months before being randomized to receive either an equipotent dose of gliclazide or to continue on glibenclamide. Diabetic control was not modified. The patients were well matched at randomization (mean age, 58 years; duration of diabetes, 8 years; 20 males; mean hemoglobin A1 [HbA1], 8.6%) and their degree of diabetic control was not altered during the trial. Free radical activity was assessed as oxidative status by plasma thiols (PSH), lipid peroxides (MDA-LM), and red blood cell superoxide dismutase activity (SOD). Platelet aggregation in whole blood to collagen (Plt-ag) was used as the measure of platelet reactivity. There were no differences between these measurements at baseline. At 3 months, the oxidative status and platelet aggregation in the gliclazide group had improved significantly compared with baseline and had also showed significant differences in all parameters when compared with the glibenclamide group. Therefore, comparing gliclazide with glibenclamide-treated patients at 3 months, we found: PSH, 458 +/- 38 versus 414 +/- 34 mumol/L, P less than .004; MDA-LM, 7.0 +/- 0.6 versus 8.3 +/- 0.8 mumol/L, P less than .0002; SOD, 152 +/- 36 versus 123 +/- 15 micrograms/mL, P less than .016; Plt-ag, 50.8 +/- 24 versus 72.3% +/- 15%, P less than .006. These changes were maintained at 6 months.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of gliclazide on platelet reactivity and free radicals in type II diabetic patients: clinical assessment. 157 14

Serum and urinary concentrations of type IV collagen and laminin were measured by enzyme-linked immunosorbent assay (ELISA) in diabetic patients and compared with normal control subjects. In diabetic patients with proteinuria or with renal insufficiency, serum and urinary concentrations of type IV collagen were higher than those of control subjects (p less than 0.005). Furthermore urinary concentrations of type IV collagen and laminin were significantly higher in diabetes, even in the absence of nephropathy, than in normal controls (p less than 0.05). Urinary concentrations of type IV collagen in patients with diabetes and microalbuminuria (0.73 +/- 0.11 mg mmol-1) were significantly higher than in diabetic patients without nephropathy (0.40 +/- 0.060 mg mmol-1) (p less than 0.025). Urinary concentrations of type IV collagen may have a role as an indicator of early diabetic nephropathy. Serum concentrations of type IV collagen in diabetic patients with retinopathy were significantly higher than in normal controls (p less than 0.025). However, urinary concentrations of type IV collagen (p less than 0.05) and serum concentrations of laminin (p less than 0.025) were significantly higher in diabetic patients than normal controls and the difference between patients with and without retinopathy was not significant.
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PMID:Serum and urinary concentrations of type IV collagen and laminin as a marker of microangiopathy in diabetes. 160 Jul 9

Collagen production has been shown to be decreased in costal cartilage from nondiabetic animals after incubation with diabetic rat serum. Since collagen was decreased to a similar degree in tissues from diabetic animals, we questioned whether altered collagen production in vivo could be related to altered production induced in vitro. Collagen and noncollagen protein production in articular cartilage from diabetic animals (production in vivo) was compared to protein production in dermal fibroblasts from non-diabetic rats exposed to serum from the same diabetic rats (production in vitro). Diabetes was induced by intravenous administration of 90 mg/kg of streptozotocin into male Sprague-Dawley rats. Cartilage was removed and incubated with [3H]-proline for 2 hours at 37 degrees C (in vivo), while fibroblasts were exposed to experimental serum from individual animals for 24 hours with addition of 5 microCi of [5-3H]-proline for the final 6 hours (in vitro). Collagen and noncollagen protein production were quantitated using purified bacterial collagenase. Collagen production in cartilage decreased to 46% (p less than .01) and noncollagen to 68% (p less than .05) of levels in control animals. Fibroblasts exposed to 2.5% diabetic serum decreased collagen and noncollagen protein production to levels of 30% (p less than .01) and 54% (p less than .05) of production in cells incubated in 2.5% normal rat serum. Correlation between defective collagen production in cartilage from individual rats and the effects of their own serum on collagen production in fibroblasts was significant (r = 0.84, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Correlation between decreased collagen production in diabetic animals and in cells exposed to diabetic serum: response to insulin. 160 33

Dupuytren's contracture is a deforming, fibrotic condition of the palmar fascia which has confounded clinicians and scientists since the early descriptions by Guillaume Dupuytren in 1831. It predominantly affects elderly, male caucasians, has a hereditary predisposition and has strong associations with diabetes, alcohol consumption, cigarette smoking and HIV infection. The major morphological features are an increase in fibroblasts, particularly around narrowed fibroblasts; a finding consistent with localised ischaemia. During ischaemia, adenosine triphosphate (ATP) is converted to hypoxanthine and xanthine, and endothelial xanthine dehydrogenase to xanthine oxidase (alcohol also mediates this change, a finding of particular relevance given the association of Dupuytren's contracture with alcohol intake). Xanthine oxidase catalyses the oxidation of hypoxanthine to xanthine and uric acid with the release of superoxide free radicals (O2-), hydrogen peroxide (H2O2) and hydroxyl radicals (OH.). These free radicals are highly reactive, with half-lives in the order of milliseconds and are toxic in high concentrations. A potential for free radical generation in Dupuytren's contracture was elicited by finding a sixfold increase in hypoxanthine concentrations in Dupuytren's contracture compared with control palmar fascia. In vitro studies affirmed the toxic effects of oxygen free radicals to Dupuytren's contracture fibroblasts, but also showed that, at lower concentrations (concentrations similar to those likely to occur in Dupuytren's contracture), free radicals had a stimulatory effect on fibroblast proliferation. Cultured fibroblasts were found to release their own O2-. These endogenously released free radicals were also found to be important in fibroblast proliferation. The collagen changes of Dupuytren's contracture were examined. The results established that fibroblast origin was unimportant, but that inhibition of type I collagen production at high fibroblast density accounted for the increase in type III/I collagen ratios observed by previous investigators. These biochemical and morphological observations throw new light on Dupuytren's contracture. They suggest that age, genetic and environmental factors may contribute to micro vessel narrowing with consequent localised ischaemia and free radical generation. Endothelial xanthine oxidase derived free radicals may both damage the surrounding stroma and stimulate fibroblasts to proliferate. Proliferating fibroblasts lay down and contract collagen in lines of stress.Progressive fibroblast proliferation and deposition of collagen is likely to encourage further microvessel narrowing with a positive feedback effect consistent with the progressive nature of the condition.
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PMID:An insight into Dupuytren's contracture. 161 55

We have undertaken an ultrastructural immunogold investigation of the distribution of type IV collagen and heparan sulphate proteoglycan (HSPG) in glomeruli from the kidneys of one normal control and three patients with diabetes mellitus and proteinuria. The sample included both diffuse and nodular diabetic glomerulosclerosis. In the control and diabetic kidneys, the type IV collagen was present predominantly on the endothelial aspect of the glomerular basement membrane (GBM), and by contrast the HSPG was found mainly on the epithelial side. In the mesangium in both control and diabetic glomeruli, type IV collagen was found predominantly in the central regions, while HSPG was mostly restricted to the region beneath the epithelial cells. Consequently, where there is a marked increase in mesangial matrix with nodule formation in diabetics there is a corresponding increase in the amount of type IV collagen but not of HSPG. Although the three diabetic patients were proteinuric, the HSPG was not decreased in the thickened GBMs.
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PMID:Diabetic glomerulosclerosis--immunogold ultrastructural studies on the glomerular distribution of type IV collagen and heparan sulphate proteoglycan. 162 58

A group of cases is presented in which dramatic repair and regeneration of periodontal tissues lost as a result of periodontitis have occurred following systemic administration of tetracycline either alone or in combination with other forms of periodontal therapy. The nature and extent of regeneration demonstrated in these patients appears to be more dramatic than what has been shown previously when more conventional forms of periodontal therapy were utilized, even including bone grafting and guided tissue regeneration. The type of repair described has been shown in many instances to be long standing and is probably not totally related to the antibacterial characteristics of tetracycline. It is suggested that the ability of this drug to inhibit collagenolytic enzymes (collagenases) may have influenced the favorable clinical results achieved. The anti-collagenolytic properties of tetracycline are being considered with increasing frequency in the treatment of other systemic diseases characterized by collagen breakdown such as corneal ulcers, rheumatoid arthritis, diabetes, and dystrophic epidermolysis bullosa. Given the highly collagenous nature of the tissues of the periodontium, this report suggests that tetracycline could be of considerable value in the treatment of some types of periodontitis.
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PMID:Enhanced repair and regeneration of periodontal lesions in tetracycline-treated patients. Case reports. 164 89

All the living molecules appear to suffer from the deleterious effects of aging, but the primary mechanisms of this inexorable evolution are still unknown. In the case of proteins, two major types of chemical reactions participate in the aging phenomena: 1) structural transformations induced by the addition of radicals by enzymic or non-enzymic reactions, 2) proteolytic cleavages. Among the reactions of the first group, the nonenzymatic glycation is the more generalized, not only in diabetic patients but also in non diabetic subjects. This glycation depends on the probabilities of encounters between circulating glucose molecules and free amino groups existing either at the N-terminal end of the polypeptide chains or on the lysyl side chains. These reactions are more frequent in the extracellular spaces and connective tissues because glucose circulates freely in these spaces, because the level of glucose is better controlled inside the cells (and even lower in diabetes mellitus), and finally because the proteins of these regions, such as the collagens, fibronectin and elastin, are relatively long lived, even if their life-span is really shorter than it was precedently believed. The binding of sugar residues to protein amino groups determines frequent modifications of structure that often make the molecule inactive. For instance, when a glucose unit binds to a lysyl radical located in the active center of an enzyme, it suppresses the activity of this enzyme. More generally, in the case of the connective tissue proteins that participate in complex supramolecular assemblies, the presence of additional radicals on some ponctual locations may interfere with the correct association of molecules. This is particularly true for basement membranes whose structure is impaired in diabetes. Glycation might also introduce abnormal cross-links between polypeptides or modify the antigenic power of some proteins and explain the formation of autoantibodies. Another property of glycated proteins is their reaction with oxygen leading to the formation of superoxide. The binding of a reducing sugar on an amino function is followed by an Amadori rearrangement that forms a ketol group. Ketols groups have the property to transmit electrons to molecular oxygen, and to forming superoxide radicals. Superoxide is capable of degrading only one protein: collagen, but it is also able to transform itself into hydrogen peroxide and hydroxyl radicals, which are far more toxic than O2-. The result of the formation of these oxygen free radicals from glycated proteins is the initiation of the degradation of several types of proteins, like the collagens.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Aging mechanisms of proteins]. 165 Dec 60

Advanced glycosylation endproducts (AGEs) are derived from the nonenzymatic addition of glucose to proteins. AGEs have been found to accumulate on tissue proteins in patients with diabetes, and their accumulation is thought to play a role in the development of diabetic complications. The finding that macrophages and endothelial cells contain AGE-specific receptors led us to examine whether mesangial cells (MCs) also possess a mechanism for recognizing and processing AGEs. Membrane extracts isolated from rat and human MCs were found to bind AGE-bovine serum albumin (BSA) in a saturable fashion, with a binding affinity of 2.0 +/- 0.4 x 10(6) M-1 (500 nM). The binding was specific for the AGE adduct, since AGE-modified collagen I and ribonuclease both competitively inhibited 125I-AGE-BSA binding to MC membranes, while the unmodified proteins did not compete. Binding of AGE proteins was followed by slow internalization and degradation of the ligand. Ligand blotting of MC membrane extracts demonstrated three distinct AGE-binding membrane proteins of 50, 40, and 30 kD. Growth of MCs on various AGE-modified matrix proteins resulted in alterations in MC function, as demonstrated by enhanced production of fibronectin and decreased proliferation. These results point to the potential role that the interaction of AGE-modified proteins with MCs may play in vivo in promoting diabetic kidney disease.
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PMID:Human and rat mesangial cell receptors for glucose-modified proteins: potential role in kidney tissue remodelling and diabetic nephropathy. 165 49


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