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)

Thromboxane A2 (TXA2) is mainly formed in thrombocytes. It promotes thrombocyte aggregation and contracts the blood vessels. TXA2 appears to be a specific physiological thrombotic agent. Synthesis of TXA2 is elevated in patients with diabetes mellitus of types I and II and in hypertensive patients. TXA2 has a half-life of about 30 s under physiological conditions. Prostacyclin (PGI2) is formed in the vessel walls. Its action is antagonistic to TXA2, that is, it inhibits platelet aggregation and dilates the blood vessels. Synthesis of PGI2 is depressed in the presence of the classical 4 main risk factors for atherosclerosis: arterial hypertension, hyperlipoproteinaemia, smoking and diabetes mellitus. PGI2 has a half-life of about 3 min under physiological conditions. Since TXA2 and PGI2 are very labile and thus extremely difficult to measure, it is at present usual to measure their stable metabolites thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha). Radioimmunological measurement (RIA) of TXB2 in plasma requires no preliminary work, but radioimmunological measurement of 6-keto-PGF1 alpha in plasma requires prior extraction and concentrating, since the concentration of 6-keto-PGF1 alpha in the plasma is usually below the detection limit of commercial RIA kits. This paper describes standardized conditions for drawing the blood sample, a simple method of extraction from plasma, and the reliability of two commercial RIA kits with 125I tracer in measuring TXB2 and 6-keto-PGF1 alpha in plasma.
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PMID:Routine measurement of thromboxane B2 and the prostacyclin metabolite 6-keto-prostaglandin F1 alpha in plasma. 377 54

Renal functional abnormalities, occurring before overt renal disease and possibly due to abnormal vascular control mechanisms, have been described in diabetes mellitus. We used intravenous (i.v.) furosemide, which stimulates renal prostaglandin (PG) synthesis and renin release, to compare these vasoactive systems in 14 diabetic and 23 normal control subjects. Using urine thromboxane B2 (TXB2) as an index of renal synthesis of the vasoconstrictor prostanoid TXA2, and urine 6keto-PGF1 alpha for the vasodilator PGI2, we found evidence of increased renal TXA2 synthesis in diabetic subjects in response to furosemide. The increased TXA2 synthesis did not occur at the expense of PGI2 synthesis, as urine 6keto-PGF1 alpha was not reduced. Increased TXB2 excretion in diabetic subjects was particularly marked in the first 10 min after i.v. furosemide. During this time, diabetic males excreted 31 +/- 6 ng of TXB2 compared with 10 +/- 1 ng for normal males (P less than 0.05), while diabetic females excreted 15 +/- 3 ng compared with 7 +/- 1 ng for normal females (P less than 0.05). Also, 6keto-PGF1 alpha excretion at 10 min was increased in diabetic subjects: males, 29 +/- 3 ng versus 19 +/- 3 (P less than 0.05); females, 33 +/- 8 versus 16 +/- 3 (P less than 0.05). The ratio of TXB2 to 6keto-PGF1 alpha tended to be higher in diabetic males.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1985 Feb
PMID:Low plasma renin activity in diabetes. Relation to urine prostaglandin excretion. 388 2

An imbalance in prostacyclin (PGI2) and thromboxane (TXA2) generation from arachidonic acid (AA) may contribute to the marked increase in susceptibility to cardiovascular disease seen in diabetics. Rats made diabetic with streptozocin, and subsequently treated with saline or insulin, yielded aortic rings that synthesized decreasing amounts of PGI2 and platelets that generated increasing amounts of TXA2 in proportion to the degree of hyperglycemia. These alterations in AA metabolism were mimicked by incubating aortic rings or platelets from normal rats in buffer containing elevated glucose concentrations. Platelets incubated in elevated glucose displayed shorter times to maximal aggregation and higher percent maximal aggregation. Incubation of tissue in a buffer made hyperosmotic with mannitol had no effect on PGI2 or TXA2 formation, or platelet aggregation. These data suggest that hyperglycemia is involved in the PGI2/TXA2 imbalance and platelet abnormalities seen in diabetes, and reinforces the importance of rigid control of blood glucose as an approach to minimizing the incidence of diabetic cardiovascular complications.
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PMID:Elevated glucose in vivo and in vitro adversely alters prostaglandin generation in rat aortas and platelets. 390 77

Basal and two hours after 600 mg acetylsalicylic acid (ASA) bleeding times were measured in 21 type I diabetic patients with retinopathy, 24 type I diabetic patients without retinopathy and 21 normal healthy volunteers. There were no significant differences either in basal or in after ASA bleeding times between these groups, but the percentage increase in bleeding time after ASA was significantly higher than normal in both diabetic groups. No correlation was found between basal--bleeding time and glucose, Hb A1 or lipid profile. TXB2 production by spontaneous blood clotting was drastically reduced by ASA in both diabetic and normal groups. Platelet hyperactivity in diabetes mellitus may be due, at least in part, to a predominance of the proaggregatory effects of TXA2 over the antiaggregatory effects of PGI2.
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PMID:Influence of acetylsalicylic acid on bleeding time and serum thromboxane B2 in diabetes mellitus type I. 400 28

Diabetic subjects tend to develop microvascular complications believed to be due to platelet hyperaggregability. This increased platelet sensitivity is though to be the result of an imbalance of PGI2 and TXA2 production in diabetes. This study sought to determine whether megavitamin E supplementation could restore PGI2/TXA2 balance in streptozotocin-diabetic rats. Endogenous release of PGI2 by isolated aorta, determined via radioimmunoassay of its stable metabolite, 6-keto-PGF1 alpha, was significantly greater (P less than 0.05) in rats receiving 100x the normal vitamin E requirement than in untreated diabetic rats. PGI2 synthesis was negatively correlated with plasma glucose levels (r = -0.87, P less than 0.05) in non-fasted rats at sacrifice. Vitamin E supplementation, at both the 10x and the 100x level, significantly depressed (P less than 0.05) thrombin-stimulated synthesis of TXA2 in washed platelet. PGI2 and TXA2 production were expressed as a ratio. Megavitamin E therapy appears to increase this ratio over that seen in the diabetic animal. The data suggest that vitamin E, at high levels, exerts an ameliorating influence of the PGI2/TXA2 imbalance of diabetes.
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PMID:Differential effects of megavitamin E on prostacyclin and thromboxane synthesis in streptozotocin-induced diabetic rats. 635 Jan 38

Diabetes is associated with a dramatic increase in the risk of thrombotic and atherosclerotic disease. The underlying factors responsible for this predisposition as well as the mechanisms involved have yet to be elucidated. Two endogenous substances, prostacyclin (PGI2) and thromboxane (TXA2), have recently been shown to possess significant vascular and thrombotic activity and are known to be altered in atherosclerosis, thrombotic conditions, and diabetes. We determined the conversion of 14C-arachidonic acid (AA) to PGI2 and TXA2 by lungs, aortas, and platelets obtained from chemically induced diabetic rats. In addition, we investigated the ability of insulin or tolbutamide to reverse these changes. Streptozotocin (STZ)-injected rats developed blood glucose levels 2-4 times that seen in normoglycemic controls. Intact perfused lungs isolated from rats beginning 7 days after STZ treatment synthesized 22-30% less PGI2 from 14C-AA. The ratio of PGI2/TXA2 was decreased in the diabetic rat lungs and was inversely proportional to plasma glucose levels at the time of death. Platelet TXA2 generation was increased 67% above control in diabetic rats while aortic PGI2 generation was decreased 28% below normoglycemic controls. Ten-day treatment with NPH insulin 20 U/kg s.c. in STZ-pretreated rats lowered plasma glucose toward normoglycemia more effectively than tolbutamide 200 mg/kg orally. Partial correction of the decreased pulmonary PGI2/TXA2 ratio seen in diabetic rats was produced by insulin and tolbutamide in proportion to their ability to lower blood glucose. At the doses employed, insulin caused aortic PI2 and platelet TXA2 generation from 14C-AA to approach that seen in mormoglycemic controls more effectively than tolbutamide.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1983 Sep
PMID:Impact of insulin or tolbutamide treatment on 14C-arachidonic acid conversion to prostacyclin and/or thromboxane in lungs, aortas, and platelets of streptozotocin-induced diabetic rats. 635 92

To counter the paucity of documention on thromboembolic disorders caused by oral contraceptives (OC), a case study is presented describing the incidence of occlusion of arteria centralis retinae in a 24-year old woman after prolonged use of an OC, Bisecurin. She had taken Bisecurin for 4.5 years and had gained 20 kg during that time, but stopped usage 1 month before admission. She was hospitalized with severe deterioration of vision in the left eye. An eye examination indicated an edematous condition of the retina and reddening of the macula. Acuity of vision value for the left eye was .01 vs. 1.0 for the right, which was confirmed by fluorescein fundus angiography. Moderately decreased antithrombin III (AT III) activity was also ascertained. Treatment consisted of immediate retrobulbar injection with Tolazolin followed by Rheomacrodex, Cavinton infusions, B1 and B12 injections, Oradexon subconjunctival injection as well as vitamin B complex, Cavinton, and Colfarit tablets and a fat-free diet. Significant improvement of the left eye condition appeared 4 weeks later. Periodic follow-ups showed the healing of the condition around the macula; however, the patient suffered permanent damage to the retina due to the arterial occlusion above and below the macula. The disturbed lipid values of metabolism were also returned to normal, as borne out by normal dextrose loading results 8 months later (glucose tolerance was abnormal during examination at admission). The estrogen and progesterone components of OCs have been shown to reduce AT III levels, shorten heparin-thrombin coagulation time, increase fibrinogen levels, decrease HDL cholesterol levels, and produce excess TXA2 (thromboxan) resulting in vasoconstriction and thrombocyte aggregation. The risk of thrombosis is 6 times higher in OC users than in nonusers, although other susceptibility factors (obesity, diabetes, hypertension) also contribute to thrombosis.
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PMID:[Arterial occlusion in the ocular fundus induced by oral contraceptives]. 651 54

We investigated the ability of platelets from two groups of diabetics type I and two groups of healthy volunteers matched of age to generate thromboxane B2 (TXB2) during spontaneous clotting of whole blood. The serum concentration of TXB2, reflecting the ability of the platelets to generate TXA2 during clotting, was measured by gas liquid chromatography. Platelets from old diabetics with more than 40 years duration of diabetes mellitus formed significantly less TXB2 than those from old healthy controls. Platelets from juvenile diabetics (9 years duration of disease) formed nearly the same amount of TXB2 as those from young healthy volunteers. The importance of these results is discussed.
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PMID:Thromboxane B2 (TXB2) formation in clotting whole blood of healthy and diabetic humans in vitro. 651 8

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

Alteration in prostanoid and TXA2 production are involved in the development of diabetic microangiopathy underlying DR. Diabetic microangiopathy is characterized by abnormalities in platelet function and increased susceptibility to thrombus formation. The synthesis of excessive amounts of PGs and TXA2 by platelets obtained from diabetic patients is underlying alteration in platelet responsiveness seen in diabetes mellitus. An associated reduction in PGI2 by endothelial blood vessels results in further disruption of the homeostatic mechanism regulating the aggregatory process. However, PGI2 behaviour in different tissues, and in blood vessels of varied calibre is yet unclear. PGI2 synthesis is restored to normal on reduction of blood glucose levels. Restoration of the synthesis of both prostanoids and PGI2 to normal, might be achieved by using drugs that inhibit prostanoid and TXA2 formation as well as by controlling glucose blood levels. Affecting the imbalance of prostanoid and TXA2 seen in diabetes might be of clinical implication in prevention and treatment of DR.
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PMID:Prostanoids and thromboxane A2 involvement in diabetic retinopathy. 676 48


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