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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to clarify whether or not arachidonic acid metabolic disorders are caused by a substrate inavailability and whether such disorders might contribute to circulatory disturbances in the diabetic myocardium. Norepinephrine induced a decrease in the conductivity of both coronary arterial bed and myocardial microcirculation in alloxan-diabetic dogs. It was markedly (p less than 0.05) attenuated both by indomethacin and acetylsalicylic acid pretreatments indicating an imbalance among the vasoactive prostanoids in diabetes. TXA2 release from the diabetic coronary rings was found to be elevated and could be normalized after the blockade of vascular adrenoceptors by phentolamine (p less than 0.05). PGI2 synthesis was also enhanced by adrenergic blockade in the diabetic arterial rings. After pretreatment with 14C arachidonic acid, in order to measure substrate availability, the arachidonic acid metabolic rate was less in the diabetic coronary arteries than in healty vessels (p less than 0.05). Ten mumol/l norepinephrine decreased arachidonic acid metabolism in the presence of prelabelled substrate in the diabetic animals, compared to an increase observed in metabolically healthy dogs. Therefore diabetes appears to diminish arachidonic acid metabolism and uptake independent of adrenoceptors and to induce an imbalance between vasoconstrictor and vasodilator cyclooxygenase products, resulting in elevated TXA2 release controlled by adrenergic mechanisms which may contribute to an impairment in myocardial microcirculation.
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PMID:Disturbed lipid metabolism in diabetic coronary vessels. 132 Jul 34

In pregnant women with severe diabetes mellitus, intrauterine growth retardation (IUGR) may occur despite hyperglycemia. Uterine blood flow may be an important factor in this process. Using pregnant streptozotocin-induced diabetic rats (pregnant STZ-diabetic rats), we evaluated functional and morphological changes in the endothelium, as well as platelet thromboxane A2 (TXA) production and their influence on uterine blood flow. Decreased basal endothelial prostacyclin (PGI2) production as well as significant attenuation of the production response to stimulus was noted, suggesting an impairment of PGI2 production. In the platelet, TXA2 production was augmented, leading to a hypercoagulable state. Decreased myometrial blood flow was documented. Scanning electron microscopy (SEM) revealed definite morphological abnormality of the endothelial cells, probably affecting the permeability to molecules, a major endothelial function. Based on these data, the endothelial derangements suggested by SEM and arachidonic acid metabolism alterations may affect fetal growth in the severe pregnant diabetic through alterations in uterine blood flow.
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PMID:Vascular wall arachidonic acid metabolism and fetal growth in the pregnant STZ-induced diabetic rat. 144 26

To investigate the possible relevance of free radicals and prostanoids to the mode of initiation and/or evolution of microangiopathy in diabetes mellitus, we measured serum lipid peroxides (LPO), an accepted index of intravascular free radicals, and plasma 11-dehydrothromboxane B2 (11-dehydro-TXB2), a stable metabolite of vasoactive thromboxane A2 released from platelets, in 95 patients with normolipidemic type 2 (non-insulin-dependent) diabetes mellitus at different stages of the disease. In general, either LPO or 11-dehydro-TXB2 was significantly greater in the patients, as a group, than in the matched controls (3.82 vs. 2.65 nmol/ml, P < 0.01 for LPO; and 17.3 vs. 5.8 pg/ml, P < 0.01 for 11-dehydro-TXB2). In patients, both LPO and 11-dehydro-TXB2 increased according to the severity of their diabetic retinopathy. A highly significant positive correlation existed between the LPO values and 11-dehydro-TXB2 in the patients (r = 0.64, P < 0.0001), while there was no such relationship in the controls (r = 0.18, P = NS). No difference in serum levels of apolipoproteins A-I, A-II, B, C-II, C-III, or E was observed between the patients and controls. Short-term glycemic control (25 cal/kg of standardized body weight/day, for 8 weeks) resulted in a small but significant reduction in LPO (4.2 vs. 4.6 nmol/ml, control; P < 0.05) without alteration in 11-dehydro-TXB2. There was a tendency towards deterioration in LPO according to the improvement in glycemic control. These results appear consistent with the view that, in addition to LPO, the release of TXA2 from activated platelet in the human circulation could be an important factor for the initiation and/or evolution of microangiopathy in diabetic patients even when they are not apparently hyperlipidemic. Further, the results of the present study emphasize the notion that more tight control of serum lipids is worthy of serious consideration in preventing the advance of diabetic microangiopathy.
Diabetes Res Clin Pract 1992 Nov
PMID:Possible relevance of lipid peroxidation and thromboxane production to the initiation and/or evolution of microangiopathy in non-hyperlipidemic type 2 diabetes mellitus. 147 57

Reduced prostacyclin (PGI2) production by the vascular wall may play an important role in the pathogenesis of vascular lesions such as atherosclerosis. The present study was undertaken to evaluate the effect of vitamin E on the production of PGI2 and other prostaglandins (prostaglandin E2 [PGE2], thromboxane A2 [TXA2], and 15-hydroxyeicosatetraenoic acid [15-HETE]) by bovine aortic endothelial cells cultured in a high concentration of glucose (300 mg/dL). Compared with endothelial cells cultured in 100 mg/dL glucose, the production of PGI2 and other prostaglandins, except 15-HETE, was significantly reduced in cultures containing 300 mg/dL glucose when stimulated by histamine, the Ca2+ ionophore, A23187, or human plasma-derived serum (PDS). The addition of vitamin E to each stimulant significantly restored the production of PGI2, PGE2, and TXA2, products of the cyclo-oxygenase pathway, in aortic endothelial cells cultured in 300 mg/dL glucose. This effect of vitamin E on the stimulation of prostaglandin production was generally specific for D-alpha-tocopherol, but not for the other vitamin E analogs tested. However, vitamin E and the stimulants had no effect on the production of 15-HETE, a product of the lipoxygenase pathway. Moreover, vitamin E alone, without stimulants, did not affect prostaglandin production in cultured bovine aortic endothelial cells. These results suggest that vitamin E may restore reduced PGI2, PGE2, or TXA2 production by bovine aortic endothelial cells cultured in a high concentration of glucose. It seems likely that vitamin E may restore depressed PGI2 production by the vascular wall in hyperglycemic conditions such as those seen in patients with diabetes mellitus.
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PMID:Vitamin E restores reduced prostacyclin synthesis in aortic endothelial cells cultured with a high concentration of glucose. 164 Aug 48

We evaluated the effects of thromboxane synthetase inhibitor, OKY-046, on urinary albumin and prostaglandin (PG) excretion in 14 patients with non-insulin-dependent diabetes mellitus (NIDDM). Urinary excretion of 6-keto-PGF1 alpha (a stable metabolite of PGI2), TXB2 (a stable metabolite of TXA2) and PGE2 in NIDDM patients was comparable with that in control subjects. However, the urinary 6-keto-PGF1 alpha/TXB2 ratio in NIDDM patients with both micro- and macroalbuminuria was significantly (P less than 0.001) lower than that in the controls. By a single administration of OKY-046 (40 mg, i.v.) to the diabetic patients, urinary TXB2 excretion significantly (P less than 0.05) decreased from 169.7 +/- 23.9 to 140.2 +/- 17.9 ng/gCr, but urinary 6-keto-PGF1 alpha and PGE2 excretion did not change significantly. The urinary 6-keto-PGF1 alpha/TXB2 ratio thus significantly (P less than 0.01) increased from 1.02 +/- 0.13 to 1.73 +/- 0.41 as associated with significant increments in urine volume (P less than 0.05), urinary sodium excretion (P less than 0.01) and creatinine clearance (P less than 0.05). Of 14 diabetic patients, 7 with macroalbuminuria (albumin index exceeding 100 mg/gCr) were orally given OKY-046 (600 mg/day) for 8 weeks. After this period, the urinary albumin index significantly (P less than 0.05) decreased from 524.9 +/- 149.6 to 317.6 +/- 90.6 mg/gCr.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Res Clin Pract
PMID:Reduction of urinary albumin excretion by thromboxane synthetase inhibitor, OKY-046, through modulating renal prostaglandins in patients with diabetic nephropathy. 207 70

Recently the beneficial effects of captopril (angiotensin-converting-enzyme inhibitor) on diabetic nephropathy, especially proteinuria, have been reported by some investigators. The mechanism whereby proteinuria is reduced, however, have not been clarified yet. The present study was undertaken to evaluate the effects of captopril on urinary albumin excretion in relation to urinary prostaglandins (PGs) excretion in patients with non-insulin-dependent diabetes mellitus (NIDDM). Captopril (37.5 mg/day) was orally administered to 13 diabetic patients for an eight-week period. A single administration of captopril (12.5 mg) was performed in the same patients. The spot urine samples were collected in the early morning and 2 hr after the single administration of captopril. The albumin index (mg/gram-creatinine) was markedly decreased in eight patients (Group A) within four weeks, but no decrease was found in five patients (Group B). Furthermore, in Group A, by the single administration of captopril urinary excretions of 6-keto-PCF1 alpha (a stable metabolite of PGI2) and PGE2 were significantly (p less than 0.05) increased while urinary TXB2 (a stable metabolite of TXA2) excretion did not change significantly. The urinary 6-keto-PGF1 alpha/TXB2 ratio, which is significantly (p less than 0.05) low in diabetic patients was significantly (p less than 0.01) increased up to the normal value in Group A. In Group B, however, there were no significant changes in urinary PGs excretion. These results suggest that captopril enhances the production of intrarenal vasodilatory PGs such as PGI2 and PGE2, which may be deeply involved in the reduction of intraglomerular capillary pressure and urinary protein excretion in diabetic patients.
Diabetes Res 1990 Mar
PMID:Effects of captopril on urinary excretion of albumin and prostaglandins in patients with diabetic nephropathy. 209 82

Urinary excretion of various renal prostaglandins was measured by radioimmunoassay and gas chromatography-mass spectrometry in children who had different degrees of metabolic control. Excretion in PGE2 in diabetic children was twice control values irrespective of the presence or absence of diabetic ketoacidosis (DKA). The urinary excretion of PGF2 alpha was significantly increased in diabetic children with ketoacidosis, but not when diabetes was well controlled. The excretion of 13, 14 dihydro-15-keto PGE2, the major metabolite of circulating PGE2, was increased in all diabetic children, and was most elevated in ketoacidosis when it averaged 10 times basal excretion. Urinary excretion of PGF2 alpha and of 6-keto-PGF1 alpha, the metabolite of PGI2, was approximately doubled in DKA compared with values from healthy subjects. Excretion of PGE2 was twice control values in children with stable diabetes, whereas the equivalent value for TXB2, the metabolite of the active vasoconstrictor TXA2, was reduced by approximately 50%. We suggest that the increased excretion of prostacyclin metabolite may result from a protective biological action on the kidney opposing other vasoconstrictor hormone activity. PGE2 appears not to be involved in this process. The highly elevated excretion of PGE2 metabolite may represent an activation of systemic PGE metabolism during DKA.
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PMID:Urinary prostaglandins in hyperglycaemic ketoacidosis of type I diabetes mellitus. 211 82

A decrease in the vitamin E content of human diabetic platelets is closely associated with the accelerated platelet aggregation and platelet prostaglandin metabolism seen in patients with diabetes mellitus. We investigated the effect of vitamin E supplementation on these abnormalities of physiological function and prostaglandin metabolism in 14 non-insulin dependent diabetics with proliferative retinopathy. ADP-induced platelet aggregation was inhibited in vitro by the addition of vitamin E in a dose-dependent manner. However, in lower concentrations considered to be physiological doses in vivo, significantly greater inhibition was observed in diabetic platelets than in the control platelets. Next, alpha-tocopheryl nicotinate was administered to diabetics at a daily dose of 600 mg. The platelet vitamin E content was restored to control levels in 13 of the 14 patients after 2-4 weeks of daily administration. The ADP-induced platelet aggregation rate, platelet thromboxane B2 (TXB2, a stable metabolite of TXA2, a vasoconstrictor production, and plasma TXB2 level were low in all 14 diabetics. In contrast, plasma 6-keto-PGF 1 alpha (a stable metabolite of PGI2, a vasodilator) was significantly increased and therefore the 6-keto-PGF 1 alpha/TXB2 ratio in plasma was restored to within normal limits. These results indicate that vitamin E may improve platelet function and prostaglandin metabolism in diabetes mellitus and may be able to provide further beneficial effects in relation to the development of diabetic vascular complications.
Diabetes Res 1990 May
PMID:Effects of vitamin E administration on platelet function in diabetes mellitus. 213 64

Sudden fissuring of an atherosclerotic plaque has been suggested as the primary trigger of transient spontaneous ischemia in both the coronary and cerebral circulation. Measurements of urinary 11-dehydro-TXB2 and 2,3-dinor-TXB2, as well as results of Aspirin trials, have suggested that episodic platelet activation at the site of this acute vascular lesion is mediated, at least partly, by enhanced thromboxane (TX) A2 biosynthesis. Thus, episodic increases in metabolite excretion have been detected in unstable angina. Aspirin (75-325 mg/day) prevents about one third of all fatal and nonfatal thrombotic events in this setting. That a similar "dynamic" thrombotic process occurs during the early phase of acute myocardial infarction is suggested by thromboxane metabolite measurements and by the results of the ISIS-2 trial showing a similar impact of short-term Aspirin therapy to that seen in unstable angina. Percutaneous transluminal coronary angioplasty is associated with transiently enhanced TXA2 biosynthesis and Aspirin-suppressable periprocedural thrombotic complications. On the other hand, both non-insulin-dependent diabetes mellitus and type IIa hypercholesterolemia are associated with a relatively reproducible and persisting abnormality of TXA2-dependent platelet function. This association is likely to reflect a systemic rather than localized stimulus to platelet activation and a continuous rather than episodic alteration. Low-dose (50 mg/day) Aspirin can largely suppress thromboxane metabolite excretion in both diseases. Thus, low-dose Aspirin and/or selective prostaglandin H2/TXA2-receptor antagonists may be important tools to test the hypothesis that TXA2-dependent platelet activation represents an important transducer of the enhanced thrombotic risk associated with these metabolic abnormalities.
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PMID:Thromboxane biosynthesis in cardiovascular diseases. 226 Jan 37

The present study was designed to determine urinary excretion of kallikrein(KAL)-kinin as well as prostaglandin (PG) E2, TXB2 and 2,3-dinor-TXB2, a major urinary metabolite of TXA2 synthesized in platelets, by specific RIAs in patients with diabetes mellitus (DM). KAL or kinin excretion in 26 type II DM did not differ from control values obtained in 18 age-matched healthy subjects (C), although DM with HbA1 greater than 11% excreted less KAL. Urinary PGE2 excretion (7.6 +/- 2.8 ng/mg creatinine, mean +/- SE) was significantly lower in DM compared to C (17.5 +/- 3.9, p less than 0.05), while DM excreted more TXB2 (0.57 +/- 0.09, p less than 0.01) and 2,3-dinor-TXB2 (0.56 +/- 0.12, N.S.) than C (0.19 +/- 0.02 or 0.33 +/- 0.01). DM with or without mild proteinuria demonstrated lower PGE2, but higher TXB2 and 2,3-dinor-TXB2 excretion. A positive correlation of TXB2/2,3-dinor-TXB2 with proteinuria was observed in this group. However, in DM with massive proteinuria over 500 micrograms/mg creatinine, TXB2 and 2,3-dinor-TXB2 excretion decreased to levels almost identical to C. As a whole, a ratio of TXB2 to PGE2 or 2,3-dinor-TXB2 in DM was significantly higher than in C. The results suggest that a relative preponderance of TXB2 to 2,3-dinor-TXB2 may indicate an augmented renal, in addition to platelet, TXA2 synthesis. An excessive vasoconstrictive and proaggregatory TXA2 renal synthesis, concomitant with a decrease in vasodilatory and antiaggregatory PGE2, may have profound effects on renal functions such as protein excretion in DM.
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PMID:Increased renal TXA2 synthesis in diabetes mellitus: simultaneous determination of urinary TXB2 and 2,3-dinor-TXB2. 233 36


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