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)

Biphasic collagen-induced platelet aggregation, resembling that induced by epinephrine, was noted in platelet-rich plasma (PRP) of 11 stroke and 1 coronary disease patients. Similar pattern of aggregation was not observed in normal PRP. The occurrence of the biphasic collagen aggregation does not appear to relate to platelet count, smoking habit, medication, or other abnormalities such as hypertension, diabetes, and elevated serum lipid levels. However, platelets of these patients were very sensitive to aggregating agents including epinephrine and adenosine diphosphate. The concentration of collagen that elicited biphasic aggregation in these platelets was too weak to aggregate platelets of normal subjects. We believe that the release threshold of these platelets is reduced to such an extent that minute amounts of collagen, which would be insufficient to induce release from normal platelets, are capable of inducing release from these platelets. Both phases of collagen induced aggregation are probably resulted from the activation of the release mechanism.
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PMID:Characterization and significance of collagen induced biphasic aggregation of human platelets. 119 59

Twenty-nine IDDM patients with borderline hypertension were randomly allocated to placebo or nitrendipine treatment. Nitrendipine was given orally at a dosage of 20 mg once daily over 4 weeks. Stimulated platelet thromboxane formation at rest and after standardized, non exhausting exercise was measured by standard methods. In addition, plasma levels of platelet factor 4 and aggregation responses to collagen and ADP were determined. In the treatment group thromboxane formation after stimulation with collagen (0.3 and 1.0 micrograms/ml) and 1 mM arachidonic acid (AA) was reduced in the resting state. Exercise induced change of thromboxane synthesis in response to 1.0 micrograms/ml collagen was significantly lower as compared to placebo (p < 0.05). In parallel, PF4 plasma levels were significantly lowered (p < 0.05). Whole blood aggregation after collagen stimulation (1.0 micrograms/ml) was reduced after 4 weeks of nitrendipine treatment, but ADP (5 microM) induced aggregation was not. These effects of nitrendipine were not seen in platelet rich plasma. In conclusion long-term nitrendipine treatment may inhibit collagen dependent platelet activation in the blood of diabetic patients with borderline hypertension.
Diabetes Res 1992 Mar
PMID:Reduced platelet thromboxane formation after long-term administration of a dihydropyridine calcium channel blocker: a prospective, double-blind, placebo-controlled study with nitrendipine in borderline hypertensive patients with IDDM-type diabetes mellitus. 128 47

The adipocyte membrane G protein pattern, beta-adrenergic receptor activity, and adenylyl cyclase were determined in adipocyte membranes of the db/db mouse, a mutant that is a model of diabetes preceded by hyperinsulinemia, hyperglycemia, and extreme obesity. These studies were undertaken to determine whether the alterations already noted in the ob/ob mouse and those in the db/db mouse are similar and related to the hormonal defects, particularly the hyperinsulinemia and hyperglycemia prevalent in these animals (cf. Ref. 11). The ADP ribosylation data show that Gs alpha was more highly labeled in the tissues of the db/db mutant than in the homozygous control, but there was no significant difference in the amount of ADP-ribose incorporated in the Gi alpha-subunits. Quantification of the proteins by immunodetection revealed that the long (46-kDa) form of Gs alpha was significantly less abundant in the db mutant than in its control, whereas there was no difference in the short (42-kDa) form. Gi alpha-peptides corresponding to Gi alpha 2 and Gi alpha 1 were both less abundant in the db mutant than in the homozygous control. These data contrasted with those obtained for ob mutants and their lean homozygous controls reported previously (4) and confirmed here. It is concluded on the basis of these studies that factors other than the hormonal status are responsible for the G protein patterns in the ob and db mutants. Differences in G protein patterns noted in between the control groups (B/Ks or B/6 homozygotes) correlated strongly with the quantitative differences in adenylyl cyclase response in the two strains.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alpha-subunits of Gs and Gi in adipocyte plasma membranes of genetically diabetic (db/db) mice. 132 37

We examined changes in guanosine triphosphate-dependent signal transduction mechanisms in the retina from the early stages of the streptozotocin-diabetic rat, a model for Type 1 (insulin-dependent) diabetes mellitus. Guanosine triphosphate binding, guanosine triphosphatase activity, and binding of (azido) guanosine triphosphate decreased significantly in the retina as early as 2 weeks after the induction of diabetes. The ability of guanosine triphosphate to inhibit forskolin-stimulatable adenyl cyclase was also abolished. These data suggest functional deterioration of G-proteins, especially Gi, in diabetic retina. Further studies using retinal rod outer segments revealed deterioration in light-sensitive, guanosine triphosphate-dependent functions of transducin in diabetic rats. Pertussis toxin-catalysed ADP ribosylation of the alpha subunit of transducin, a heterotrimeric G-protein of rod outer segments, was also reduced in diabetes. No functional effects were seen in purified subunits of transducin subjected to non-enzymatic glycation in vitro. On the other hand, incubation of non-diabetic rod outer segments with (12-0-tetradeconyl) phorbol-13-acetate, a protein kinase C agonist, in the presence of magnesium and adenosine triphosphate resulted in the reduction of guanosine triphosphate-binding and hydrolysis, thus indicating that protein kinase C may be involved in the regulation of these activities. The significance of these observations in the early visual abnormalities associated with diabetes is discussed.
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PMID:Functional alterations of G-proteins in diabetic rat retina: a possible explanation for the early visual abnormalities in diabetes mellitus. 132 50

All of the components of the neuropeptide vasoactive intestinal peptide (VIP) signal transduction system were underexpressed in rat prostatic membranes 6 weeks after streptozotocin-induced diabetes. Binding studies with [125I]VIP showed decreases of 86% and 62% in the binding capacity of the high and low affinity classes of VIP receptors in diabetes. Affinity labeling experiments indicated that the main form of VIP receptor was 51 kilodaltons in control rats and 45 kilodaltons in diabetic animals. The efficacy of VIP and forskolin in stimulation of adenylyl cyclase activity as well as the potentiating effect of GTP on VIP action were also reduced in diabetes, as was the expression of the alpha-subunit of the guanine nucleotide-binding regulatory proteins Gs and Gi (studied by ADP ribosylation with cholera and pertussis toxins). Gi function was lost in diabetes, as assessed with experiments on guanyl-5'-yl-imidodiphosphate potentiation of forskolin activity. These disturbances together with previous findings argue for VIP playing a role in the diabetic neuropathy of the genitourinary tract.
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PMID:The effect of streptozotocin diabetes on the vasoactive intestinal peptide receptor/effector system in membranes from rat ventral prostate. 132 26

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

Diabetes is known to be associated with an increase in aldose reductase activity, platelet hyperaggregability, lipid peroxidation, and cataract formation. A molecule, D-myo-inositol 1,2,6-trisphosphate (PP-56), derived from phytic acid, could in principle, by supplying myoinositol to tissues and acting as an antioxidant, counteract some of the manifestations of diabetes. Thus, the effects of PP-56 on platelet aggregation, fatty acids, and polyols were investigated in uncontrolled streptozotocin-induced diabetes in rat in relation to cataract and lipid peroxidation. A decrease in the response of platelet aggregation to thrombin and ADP (P less than 0.05, P less than 0.001) and in the level of sorbitol and the ratio sorbitol/myo-inositol (P less than 0.01) in platelets was observed in the rats treated by PP-56 for 7-8 weeks. These beneficial effects were associated with an incidence of cataract reduced by 26 to 44% (P less than 0.05 to P less than 0.001) depending on the duration of treatment. They were also accompanied by a significant lower plasma level of malondialdehyde (P less than 0.05), and, more markedly, of conjugated dienes (P less than 0.001) as well as an increase in platelet lipids of the 20:4(n-6)/20:3(n-6) ratio, an index of delta 5 desaturase activity. PP-56 appears to modulate fatty acid desaturases and aldose reductase in platelets and delay by a few weeks the development of cataract in this acute model of diabetes.
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PMID:Effect of D-myo-inositol on platelet function and composition and on cataract development in streptozotocin-induced diabetic rats. 138 35

We propose new hypotheses for the mechanisms of streptozotocin (STZ) and alloxan inducing experimental diabetes in animals. STZ is transported into pancreatic beta cells through glucose transporter in the cell membranes and attacks mitochondria. Mitochondrial ATP generation is inhibited and the resulting high concentration of intracellular ADP causes its degradation providing hypoxanthine, a substrate of xanthine oxidase (XOD) whose activity is intrinsically very high in beta cells. Then, XOD-catalyzing reaction is proceeded as proved by increased formation of uric acid and O2- radicals are produced, but beta cells are inefficient to scavenge these radicals because of their extremely low activity of superoxide dismutase. On the other hand, STZ directly activates XOD and enhances O2- generation. Consequently, pancreatic beta cells are dually suffered from O2- radicals or probably hydroxyl radicals derived from the former when exposed to STZ. Allopurinol, an inhibitor of XOD, can protect animals from the diabetogenic effect of STZ. In pancreatic beta cells, alloxan anion radicals are generated from alloxan probably mediated by the action of microsomal cytochrome P-450 system. These radicals have long half-life and directly damage DNA in vitro. The widely accepted hypothesis that the cause of alloxan-induced diabetes is attributable to O2- radicals formed from alloxan is excluded, because alloxan itself shows a very potent scavenging effect to O2- radicals. Therefore alloxan anion radicals seem to be directly related to the incidence of diabetes by alloxan.
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PMID:[New hypotheses for the mechanisms of streptozotocin and alloxan inducing diabetes mellitus]. 148 45

1. To investigate the effect of experimental diabetes on the P2y purinoceptor responses of pancreatic beta-cells and vascular bed, we used adenosine-5'-O-(2-thiodiphosphate) (ADP beta S), a potent and stable P2y agonist. This work was performed in the isolated perfused pancreas of the rat. 2. Diabetes was induced by streptozotocin (66 mg kg-1, i.p.). Five weeks after the induction of diabetes, on the day of pancreas isolation, the animals displayed marked hyperglycaemia (37.6 +/- 2.7 mM). Age-matched rats were used as controls. 3. Insulin response to a glucose stimulation from 5 to 10 mM was completely lost and stimulation of insulin release by the sulphonylurea, tolbutamide (185 microM), was drastically impaired in the diabetic pancreas (maximum responses were 1.5 +/- 0.4 and 7.0 +/- 1.4 ng min-1 for diabetic and age-matched rats respectively). 4. In contrast, in the diabetic pancreas ADP beta S (15 microM), infused in the presence of glucose 5 mM, elicited an immediate and significant insulin release similar to that observed in the age-matched pancreas (maximum responses were 7.6 +/- 1.5 and 6.7 +/- 1.3 ng min-1 respectively). This ADP beta S stimulating effect occurred independently of the glucose concentration (5, 8.3 and 28 mM) in the diabetic pancreas. On pancreatic vascular resistance, ADP beta S induced a similar vasodilatation in diabetic and age-matched rats. 5. In conclusion, ADP beta S retains its insulin stimulatory and vasodilator effects in experimental diabetes; P2y purinoceptors could therefore be considered as a new target for the development of antidiabetic drugs.
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PMID:P2y purinoceptor responses of beta cells and vascular bed are preserved in diabetic rat pancreas. 150 44

Platelets from diabetic humans and animals are hypersensitive to ADP. The hypersensitivity to ADP of platelets from diabetic rats occurs independently of activation of the arachidonate pathway or release of dense granule contents. During platelet aggregation by ADP, fibrinogen binds to its receptor on platelets. We examined if the hypersensitivity to ADP of platelets from diabetic rats is associated with enhanced early binding of fibrinogen to its receptor on these platelets. Fibrinogen association with platelets from rats with spontaneous or streptozotocin-induced diabetes was significantly greater 10 s or 1 min after addition of ADP (10 microM) than with platelets from their corresponding control rats. Since enhanced fibrinogen association occurred with platelets from insulin-treated rats with spontaneous diabetes, and from rats with streptozotocin-induced diabetes that did not receive insulin, the enhanced fibrinogen binding is likely due to the diabetic state rather than to the administration of insulin or the mechanism responsible for the diabetes. Therefore, enhanced early fibrinogen association with platelets from diabetic rats is associated with their hypersensitivity to ADP.
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PMID:Hypersensitivity to ADP of platelets from diabetic rats associated with enhanced fibrinogen binding. 155 39


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