Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hemovascular abnormalities encountered in diabetes include platelet alterations, shifts in prostaglandin metabolism and disorders of fibrinolysis. Diabetes is thus associated with increased platelet adhesiveness, increased platelet aggregation with hypersensitivity to proaggregants, increased plasma levels of beta-thromboglobulin and platelet factor 4 as an expression of platelet hyperactivity, increased levels of thromboxane A2 (TXA2) and prostacyclin (PGI2), and reduced levels of tissue plasminogen activator (t-PA). It is not clear which, if any, of these abnormalities are generated by chronic hyperglycemia and can be corrected by adequate glycemic control. Studies with gliclazide have demonstrated that it exerts hemovascular effects which can be valuable to patients. Thus, treatment with gliclazide leads to a decrease in platelet adhesiveness and aggregability. This treatment also reduces thromboxane levels and increases TPA levels. The mechanisms of action of gliclazide are not fully known but it has been demonstrated that its antiplatelet action is independent of its hypoglycemic activity and is not accompanied by clinical abnormalities of blood clotting. The mechanism of direct action on platelet activity may be mediated by inhibition of activated glycogen synthetase, activation of adenylate cyclase, modulation of arachidonic acid release from platelet membranes, stimulation of PGI2 production, and inhibition of the proaggregant action of TXA2. Thus, gliclazide not only has a hypoglycemic action but also improves hemovascular parameters in type 2 diabetes when used at normal therapeutic doses.
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PMID:Hemobiological activity of gliclazide in diabetes mellitus. 179 71

During storage of platelet concentrates under routine blood banking conditions a gradual increase takes place in the degree of platelet activation. Studies were designed to determine whether the addition of forskolin, a direct activator of platelet adenylate cyclase and inhibitor of platelet activation, could reduce some of the deleterious changes occurring during a 10-day storage period at 20 degrees to 24 degrees C. Forskolin was added to the platelet-rich plasma before preparation of the platelet concentrates. Dose-effect studies in which 0.5, 5, and 50 mumol/L forskolin were compared indicated that 5 mumol/L forskolin was the optimal concentration for the reduction of platelet activation over this period as assessed by measuring the release of beta-thromboglobulin and the formation of thromboxane B2. It was determined that cyclic adenosine monophosphate levels were increased approximately fourfold by 5 mumol/L forskolin and maintained at a high level for at least the first 48 hours. These results show that the presence of forskolin inhibits the activation of platelets during storage.
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PMID:Effect of forskolin on the maintenance of platelet properties during storage. 376 Jun 76

Increased platelet reactivity has been suggested in the pathogenesis of both arteriosclerosis and diabetic microangiopathy. Therefore, platelet function and platelet enzyme activities were assessed in a large group of 357 diabetics (256 patients with IDDM, aged 16-49 and 101 patients with NIDDM, aged 50-78) and 163 matched controls, and related to photographically documented retinopathy (Rd) and to peripheral vascular disease (PVD) as well as to plasma levels of von Willebrand factor (VIII R:Ag) as an indicator of endothelial damage. Patients with IDDM had increased platelet aggregation (PA, expressed as microM ADP threshold concentration) before Rd was detectable in comparison to control subjects (P less than 0.01). PA was further increased in patients with advanced Rd (P less than 0.01), whereas 20 newly diagnosed diabetics with IDDM exhibited normal PA. Patients with minimal Rd did not differ from patients without Rd. Plasma beta-thromboglobulin (reflecting platelet consumption in vivo) was enhanced significantly in patients with Rd only (P less than 0.05), as was malondialdehyde (MDA) production of platelets (as a measure of platelet endoperoxide formation). Factor VIII-related antigen in plasma was already increased in patients without Rd (P less than 0.05), yet more so in patients with Rd (P less than 0.01). Prostacyclin-stimulated adenylate cyclase activity (ACA) of platelets (as an antiaggregatory enzyme system) was twice as high in diabetics with advanced Rd compared with patients without Rd and with controls (P less than 0.01). Significant correlations were found between PA and plasma F VIII R: Hg, MDA production, and ACA of platelets.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Platelet enzyme activities in diabetes mellitus in relation to endothelial damage. 608 25

Platelet aggregation, beta-thromboglobulin levels and the platelet adenylate cyclase activity (expressed as increase of cAMP levels) were determined in blood samples from healthy control subjects and from diabetic patients with and without microangiopathy. Patients with diabetic microangiography showed significantly higher beta-thromboglobulin levels, an increased tendency to platelet aggregation, and higher cAMP levels in platelet-rich plasma after incubation with PGI2. The findings were interrupted by the assumption of an increased turn-over of platelets which might be a consequence of the microvascular disease.
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PMID:Increased platelet adenylate cyclase activity ion diabetic patients with microangiography. 617 51

Two groups of diabetic patients in poor metabolic control were followed prospectively for platelet function in the course of adequate insulin therapy. All 8 ketoacidotic and 38 nonacidotic, but markedly hyperglycemic, patients showed decreased platelet aggregation at the time of entering the hospital in comparison to subsequent controls. Platelet adenylate cyclase activity rose during the observation periods significantly. Changes of beta-thromboglobulin plasma levels were not uniform. These data give evidence for a metabolic factor which modifies platelet functions to a considerable degree.
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PMID:Influence of metabolic control on platelet functions in diabetic mellitus. 627 78