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)

To increase knowledge about the defense mechanisms of pancreatic beta-cells exposed to acute injury, the patterns of protection exerted by 3-aminobenzamide and nicotinamide against the effects of streptozotocin have been studied in vivo and in vitro. It was found that 3-aminobenzamide, a strong inhibitor of the NAD-consuming nuclear enzyme poly(ADP-ribose) synthetase, is maximally effective against streptozotocin-induced diabetes in the rat when administered 45-60 min after the beta-cytotoxic agent, unlike nicotinamide, which exerts best protection when given very close to streptozotocin. A partial protection is still afforded by 3-aminobenzamide administered as long as 120 minutes after streptozotocin. In isolated islets, each protective agent, if added to the incubation medium 20 or even 40 minutes after the exposure of the islets to streptozotocin, is able to partially prevent the effects of the damaging drug on glucose-stimulated insulin release. However, best protection in vitro is obtained when either 3-aminobenzamide or nicotinamide is added simultaneously with the toxic agent. Our results support the concept that the reversibility of streptozotocin-induced acute damage in beta-cells depends on the preservation of intracellular NAD pools during critical time intervals. This can be achieved by two different partially overwhelming mechanisms: a) early stimulation of NAD biosynthesis (prevailing effect of nicotinamide) and b) strong inhibition of poly ADP-ribosylation activity (main effect of 3-aminobenzamide).
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PMID:Protection by 3-aminobenzamide and nicotinamide against streptozotocin-induced beta-cell toxicity in vivo and in vitro. 214 20

Alterations in platelet function have been observed in a number of diabetic states. Increased responsiveness to platelet-aggregating agents in diabetes associated with increased catecholamine production and/or turnover suggested that heightened sympathetic activity may contribute to this increased platelet aggregation response. To investigate this possibility, we made male Wistar-Furth rats diabetic with streptozotocin and treated them either with adrenergic inhibitors (clonidine, yohimbine, reserpine) or saline. After 2 weeks, arterial blood samples were collected in 3.8% sodium citrate or acid citrate dextrose (ACD). Platelet-rich plasma (PRP) was prepared, and platelet aggregation studies were conducted directly or conducted on washed platelets prepared from PRP collected with ACD. Platelet aggregation in response to ADP by PRP was reduced while the rate of disaggregation was increased in platelets from diabetic animals when compared to controls. However, platelet aggregation in response to ADP in washed platelets was increased in diabetic animals when compared to controls. Clonidine, reserpine and yohimbine significantly decreased the diabetes-induced increase in maximum aggregation. Thrombin-induced aggregation was not altered by diabetes or any of the treatments. The platelet size was increased in the diabetic animals and was decreased toward controls by clonidine, reserpine and yohimbine treatment. These studies suggest that diabetes increases platelet aggregation response in diabetic rats, and that blockage or suppression of adrenergic activity reverses or attenuates the diabetes-induced hypersensitivity to ADP.
Diabetes Res Clin Pract 1990 Jul
PMID:Platelet aggregation and disaggregation in the streptozotocin induced diabetic rat: the effect of sympathetic inhibition. 214 2

The urinary bladder depends on intracellular ATP for the support of a number of essential intracellular processes including contraction. The concentration of ATP is maintained constant primarily via the rapid transfer of a phosphate from creatine phosphate (CP) to ADP catalyzed by the enzyme creatine kinase (CK). Since muscular pathologies associated with diabetes are in part related to intracellular alterations in metabolism, we have characterized the CK activity in both skeletal muscle and urinary bladder from control and streptozotocin-diabetic rats. The following is a summary of the results: 1) Bladder tissue from control rats showed linear kinetics with a Vmax = 390 nmoles/mg protein/min, and a Km = 275 microM. 2) Urinary bladder tissue isolated from diabetic rats displayed biphasic kinetics with Vmax = 65 and 324 nmoles/mg protein/min, and Km's = 10 microM and 190 microM respectively. 3) Skeletal muscle isolated from control rats showed linear kinetics with an approximate Vmax of 800 nmoles/mg protein/min and a Km of 280 microM CP. 4) Homogenates of skeletal muscle from diabetic rats showed complex kinetics not separable into distinct component forms. 5) The Km for ADP for both skeletal muscle and bladder was approximately 10 microM. These studies demonstrate that whereas bladders isolated from both control and diabetic rats possess a low-affinity isomer(s) of CK with similar maximum enzymatic activity, there is a high affinity isomer present within the urinary bladder muscle of diabetic rats that is not present in bladder tissue isolated from control rats. Skeletal muscle isolated from both diabetic and control rats exhibited a maximal activity 2 to 3 times higher than that of the bladder.
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PMID:Creatine kinase activity of urinary bladder and skeletal muscle from control and streptozotocin-diabetic rats. 214 63

Platelet intracellular Ca2+ concentration ([Ca2+]i) and its response to stimuli (ADP and thrombin) were studied in 15 insulin-dependent and 22 non-insulin-dependent diabetes mellitus patients with the fluorescent probe Fura 2. The activity of Ca2(+)-ATPase and Na(+)-K(+)-ATPase, membrane fluidity, and cholesterol and phospholipid content were also determined in platelet membranes. Compared with control subjects, diabetic patients showed 1) increased platelet [Ca2+]i in the resting state, 2) higher Ca2+ levels after stimulation with thrombin and ADP, due entirely to increased resting concentrations, 3) reduced activity of Na(+)-K(+)-ATPase, 4) increased activity of Ca2(+)-ATPase, 5) higher fluidity of the platelet membrane, and 6) increased membrane concentration of total phospholipids. Na(+)-K(+)-ATPase activity was inversely related to platelet [Ca2+]i in each group studied, whereas Ca2(+)-ATPase activity was positively correlated with intracellular Ca2+ levels. The data obtained in diabetic subjects suggest an abnormality in Ca2+ and Na+ transport across the platelet membrane that might be responsible for the reported platelet hyperreactivity to stimuli in diabetes.
Diabetes 1990 Jul
PMID:Altered cellular Ca2+ and Na+ transport in diabetes mellitus. 216 3

The thrombocyte reactivity and values of HbA1c, serum cholesterine and creatinine have been examined in 121 insulin-treated and 70 not-insulin-treated diabetic patients and in 98 healthy persons. The thrombocyte functions of patients ranged according to the microangiopathic complications and of control groups matched according to age and sex were analysed with comparative statistics. Positive correlation was found in diabetes between the serum creatinine and cholesterine levels and the aggregating agents' (adrenaline, ADP, and collagen) limit concentrations (p less than 0,05-0,001). Close correlation seems to be between the worsening of renal functions and the decrease of thrombocyte sensitivity in diabetes: The hypercholesterinemia observable in nephropathic diabetes did not lead to the hyperaggregability known in familial hypercholesterinemia. Thus it appears likely that the cholesterine-level increase in the serum does not influence directly, but rather by the effects in connection with its origin, differently the thrombocyte reactivity.
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PMID:[Correlation of thrombocyte reactivity and serum levels of HbA1c, cholesterol and creatinine in diabetes mellitus]. 217 10

Interleukin-1 beta (IL-1 beta) has been implicated in the pathogenesis of insulin-dependent diabetes mellitus. In the present study we have investigated the effects of IL-1 beta on glucose metabolism in clonal HIT-T15 beta cells. In the short-term (1 h), 25 U/ml IL-1 beta significantly increased the rates of insulin release and glucose utilisation, but not glucose oxidation. In contrast, after 48 h, IL-1 beta inhibited insulin release and glucose utilisation and oxidation. By assaying enzymes (hexokinase, glucokinase, pyruvate dehydrogenase, glucose 6-phosphatase) and nucleotides (ATP, ADP) associated with the regulation of glycolysis and glucose oxidation, we conclude that the inhibitory effects of IL-1 beta may be due to impaired glucokinase activity.
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PMID:Interleukin-1 beta inhibits glucokinase activity in clonal HIT-T15 beta-cells. 219 15

In 18 patients with type I diabetes the effect was studied of 10 days of Indobufen administration in daily doses of 400 mg on the activation and function of platelets. Spontaneous and ADP and adrenaline-induced aggregation, adhesiveness, platelet factors 3 and 4, and generation of malonyldialdehyde (MDA) in platelets were investigated. The results were compared with similar results in the same group prior to the treatment and in a control group of 19 healthy subjects. Highly significant inhibition was noted of spontaneous inhibition and that evoked by adrenaline and ADP, and a considerable reduction of MDA generation by platelets. These results indicate that the new platelet inhibitor--Indobufen, effectively inhibiting platelet activation and function may prevent development of thrombotic complications of diabetes.
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PMID:[Activation and functions of blood platelets in patients with diabetes mellitus type 1 before and during the treatment with indobufen]. 221 38

An increased platelet-vessel wall interaction plays an important role in most forms of cardiovascular disease. In healthy arteries, the vascular endothelium prevents platelet adhesion and aggregation. As a mediator of this protective function, the endothelium produces prostacyclin, endothelium-derived nitric oxide and tissue plasminogen activator. Cardiovascular risk factors such as hypertension, hyperlipidemia and diabetes are associated with an increased platelet activation and with decreased antithrombotic properties of the blood vessel wall. The available inhibitors of platelet function interfere only with one of various mechanisms of platelet activation and of the platelet-vessel wall interaction. Prostaglandin inhibitors, such as aspirin and newer, more specific inhibitors, prevent the production and/or the effect of thromboxane A2 on platelets and the blood vessel wall. Other drugs interfere with the effect of adenosine diphosphate on platelets, or they increase intracellular concentration of cyclic GMP or AMP in platelets and vascular smooth muscle cells. The protective effects of platelet inhibitors in primary and particularly in secondary prevention of cardiovascular diseases have been documented in numerous studies. The successful clinical use of these substances, however, requires a selective prescription of the drugs in patients with cardiovascular disease.
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PMID:[Thrombocyte inhibitors in cardiovascular therapy]. 221 49

Dilution of thrombocyte-rich blood plasma (down to 2.5 x 10(8) thrombocytes/ml) enabled to avoid an irreversible phase of the ADP-induced thrombocyte aggregation; the reversible phase of aggregation was followed by deaggregation. The reversible aggregation of thrombocytes was studied in healthy persons and patients with diabetes mellitus within wide ranges of ADP concentrations (including 10 microM) using the diluted blood plasma. Thrombocytes of the patients with diabetes mellitus of the I and II types were found to be 1.6- and 2.33-fold more sensitive to the ADP aggregating effect as compared with thrombocytes of healthy persons. The elevated rate of thrombocytes aggregation in diabetes mellitus appears to be related to early decrease in activity of thrombocyte guanylate cyclase and to its ability to be activated.
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PMID:[ADP-induced aggregation of human platelets in diabetes mellitus]. 223 25

Many case-control studies have suggested that increased platelet aggregation (PA) could be involved in the pathogenesis of diabetic microangiopathy. However, longitudinal data are needed to support this hypothesis. We consider here such an approach in the placebo group (93 diabetic patients) of a controlled clinical trial on the effect of PA inhibitors in the treatment of diabetic retinopathy (Damad program). We have measured spontaneous PA and PA induced by ADP, collagen and arachidonic acid before treatment and yearly during a 3-year period. The assessment of retinopathy was based on the changes in the number of microaneurysms present in the macular field as seen on fluorescein angiograms during follow-up. PA was estimated by maximal decrease in optical density. The lowest ADP concentration still able to induce irreversible aggregation was also determined. No significant correlations between any baseline PA measurements and end point criterion were found (all correlation coefficients lower than 0.20). No significant changes in mean PA were observed during follow-up. Within-subject variation of PA was markedly large accounting for 61% to 98% of the total variance of various measurements. Allowances for the main characteristics of diabetes made no substantial difference to the results. These negative findings can be partly attributed to the lack of reliability of PA tests. In our study, we conclude that PA tests are not useful measures for the prediction of evolution of background diabetic retinopathy.
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PMID:Does increased platelet aggregation have a prognostic value in the deterioration of background diabetic retinopathy? The Damad Study Group. 227 May 29


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