Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In one third of patients who suffered an infarction NIDDM and arterial hypertension are present. In the absolute majority of patients with IHD, as apparent from the IRI and C-peptide response after a glucose load, hyperinsulinism is present. The blood sugar response can have the character of diabetes or of impaired glucose tolerance, the curve may be very flat or normal while the IRI and C-peptide response are excessive. Hyperinsulinism has a hypersecretory origin as suggested by the concurrently elevated C-peptide level but also reduced insulin utilization in the liver and peripheral target organs. Hyperinsulinism is thus a regular associated phenomenon of IHD and is a special risk factor independent on hyperglycaemia and associates with the other main risk factors of IHD such as arterial hypertension, HPLP (android obesity), hyperglycaemia (NIDDM) and hirsutism as a manifestation of a hyperandrogenic state in the female organism with the syndrome of polycystic ovaries. Hyperinsulinism plays an indirect role in the pathogenesis of coronary syndrome via the main risk factors (5H syndrome--hyperinsulinism, hypertension, HPLP, hyperglycaemia, hirsutism) and also directly by its action on endothelial paracrine mechanism of the coronary circulation where in the early stage vasoconstrictor factors predominate (endothelin-1, PGF2-alpha) over physiological vasodilatating factors (EDRF-NO, PGE2, PGI2) and this leads then to functional spasms. It seems that also the coronary X syndrome develops very frequently on the background of the hormonal metabolic X syndrome or the 5H syndrome.
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PMID:[Hyperinsulinism and the coronary syndrome]. 149 68

Human plasma-derived serum (PDS) stimulated the production of 6-keto-PGF1 alpha (a stable metabolite of PGI2) by cultured bovine aortic endothelial cells. The stimulation was both time- and dose-dependent. The main prostacyclin stimulatory activity (PSA) in human PDS remained biologically active after dialysis and was inhibited by the simultaneous addition of heparin. The maximum inhibition of PSA was obtained with 10 micrograms/ml heparin. PDS obtained from patients with non-insulin-dependent diabetes mellitus (NIDDM, n = 24) showed significantly less PSA than that from the control subjects (n = 11). A decrease in PSA was also found in diabetic patients using dialyzed PDS. The PSA in human PDS had a specific binding affinity to heparin-agarose and the bound PSA was eluted by a linear gradient of NaCl, which showed two major PSA peaks at 1.0 and 1.5 M NaCl. The dialyzed, mixed PDS from patients with NIDDM and the control subjects was independently applied to a heparin-agarose column and eluted by a linear gradient of NaCl. Comparing the PSA in each peak between the diabetic and the control dialyzed PDS, the PSA at 1.5 M NaCl was markedly decreased in the diabetic patients, but the PSA at 1.0 M NaCl did not change significantly. These observations suggest that the decreased PSA in human diabetic PDS may result mainly from the decrease in the activity of a specific non-dialyzed factor(s) which can bind to heparin. The decreased PSA in serum seems to be responsible in part for decreased PGI2 synthesis by the vascular wall of diabetics.
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PMID:Partial purification of serum prostacyclin stimulatory activity by heparin-agarose column; abnormality detected in diabetics. 160 Aug 48

Conflicting data have been reported about the impaired sensitivity to the inhibitory effect of prostacyclin (PGI2) in platelets from patients with diabetes. In the present paper we investigated binding of and sensitivity to PGI2 of platelets from insulin dependent (IDDM) (n = 9), non insulin dependent (NIDDM) (n = 8) diabetics and two groups of ten healthy subjects of equivalent age in relation to platelet lipidic content. Platelet sensitivity to PGI2 (PGI2 IC50) was found not significantly changed in diabetics as compared to controls; similarly, no significant differences of the number of high affinity receptors for PGI2 in platelets from patients with IDDM and NIDDM were observed. Platelet sensitivity to PGI2 and PGI2 receptors were found to be significantly related to platelet cholesterol content (r = 0.89, p less than 0.001 and r = -0.80, p less than 0.001 respectively). In conclusion platelet PGI2 receptor changes are not detectable in diabetics in good metabolic control, but could take place when platelet lipid composition is altered.
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PMID:Human prostacyclin platelet receptors in diabetes mellitus. 175 6

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

Reduced prostacyclin (PGI2) generation by the vascular wall shows a close relationship with the development of atherosclerosis. The present study found plasma-derived serum (PDS) to contain an activity which stimulated PGI2 production by cultured bovine aortic endothelial cells. Diabetic and aged patients with atherosclerotic disease were examined for abnormalities in that stimulatory activity in PDS. PDS obtained from both diabetics (NIDDM) and aged patients showed a significant reduction in the stimulation of PGI2 production by cultured bovine aortic endothelial cells compared with age-matched controls and young healthy volunteers, respectively. It was suggested that the reduced PGI2 stimulatory activity in PDS may be one of the pathogenic mechanisms of vascular lesions such as atherosclerosis in diabetics and aged humans.
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PMID:Reduced stimulatory activity on prostacyclin production by cultured endothelial cells in serum from aged and diabetic patients. 264 13

In the present study the effects of a short term intensive glycaemic control obtained with subcutaneous insulin therapy on lipids and apoprotein levels, platelet aggregation, platelet sensitivity to prostacyclin and platelet thromboxane production were investigated in 20 patients with type 2 diabetes and vascular disease. In 11 out of the 20 patients there was a significant improvement of glycaemic control (fructosamine reduction). Only with tight improvement of glycaemic control there was significant change in the concentration of ADP and collagen required to produce 50% of the maximum aggregation wave response, in the responsiveness of platelet to PGI2 and in the TxB2 synthesis. Lower Apo B levels were also shown in the tight control group suggesting that Apo B changes may have influenced platelet aggregation and thromboxane synthesis.
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PMID:Platelet function in patients with type 2 diabetes mellitus: the effect of glycaemic control. 266 42

Toxemia of pregnancy is a perplexing clinical problem that has defied accurate elucidation of its etiology because the disorder does not occur in undisturbed lower mammalian species that are currently used as animal models of reproductive physiology. We propose that toxemia of pregnancy occurs as the end stage human fetal-placental unit response to decreased maternal uterine blood flow, and that this fetal-placental unit response may be unique to the human species. The human fetus increases insulin secretion in response to progressive intrauterine asphyxia, which may result in decreased fetal-placental prostacyclin production (a vasodilator and inhibitor of platelet aggregation) and increased fetal-placental thromboxane A2 production (a vasoconstrictor). This could result in increased uteroplacental perfusion pressure, maternal hypertension, and increased maternal platelet aggregation. We also suggest that women who develop idiopathic toxemia of pregnancy are at increased risk for adult onset diabetes later on in life because they have a mild derangement in glucose-insulin homeostasis during their reproductive years that results in increased uterine vascular damage, that leads to decreased uterine blood flow, and ultimately the fetal hyperinsulinemia-prostaglandin pressor release mechanism. Therefore, prevention of toxemia may be possible by correction of mild derangements in glucose-insulin receptor homeostasis before conception occurs.
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PMID:Theory of the etiology of human toxemia of pregnancy: fetal hyperinsulinemia as a compensatory response to decreased uterine blood flow. 330 29

Prostacyclin is degraded in human plasma in vitro with an average half-life of 10 minutes. The degradation in plasma of patients suffering from type II diabetes mellitus is significantly enhanced. However, the inactivation of prostacyclin in plasma in patients with clinical manifestations of atherosclerosis, such as peripheral vascular disease, is unchanged. Methodological studies reveal that storage of plasma at various temperatures up to investigation, repeated freezing and thawing, as well as the addition of thromboxane-synthetase inhibitors do not exert any effect on plasmatic degradation of PGI2. In addition, no differences are found in plasmatic degradation in diabetics in accordance with the mode of treatment. The presence of a factor in human plasma in diabetics capable of increasing PGI2 degradation or the loss of a possible stabilizer could be one further important parameter, amongst others responsible for the development of either macro- or microangiopathy in diabetes mellitus.
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PMID:[Accelerated degradation of prostacyclin in diabetic plasma--a further factor in the impairment of hemostatic balance?]. 390 20

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

Prostacyclin (PGI2) is the most potent endogenous inhibitor of platelet aggregation yet discovered. Thromboxane (TXA2) promotes aggregation and degranulation of platelets. It is hypothesized that an homeostasis exists between these pathways that is protective against vascular damage and is disturbed in several diseases such as diabetes. Circulating levels of PGI2-TXA2 in 35 patients with adult onset diabetes and 15 controls have been assayed. Twenty patients had background retinopathy, and 15 had proliferative retinopathy. Circulating levels of PGI were found to be elevated in 9/15 patients with proliferative diabetic retinopathy, 2/20 diabetic patients with background or no retinopathy, and 0/15 controls. PGI levels may correlate, therefore, with the severity of the retinopathy.
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PMID:Circulating prostacyclin and thromboxane levels in patients with diabetic retinopathy. 675 Apr 95


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