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

The relative contribution of atrial natriuretic peptide (ANP) and vasodilatory prostaglandins to hyperfiltration in Wistar rats with experimental diabetes was studied 6-8 wk after streptozocin injection. Plasma levels of immunoreactive ANP were significantly higher (P less than 0.01) in hyperglycemic diabetic (72.9 +/- 11.7 pg/ml) than in normoglycemic diabetic (44.8 +/- 8.6 pg/ml) or nondiabetic (40.0 +/- 6.8 pg/ml) rats. Blocking endogenous ANP by specific ANP-antiserum infusion reduced significantly (P less than 0.01) glomerular filtration rate (GFR) and renal plasma flow (RPF) of hyperglycemic rats compared with preinfusion values (1.23 +/- 0.06-1.02 +/- 0.04; 2.87 +/- 0.25-2.40 +/- 0.10 ml.min-1.100 g-1, respectively). However, correction of hyperfiltration and hyperperfusion was only partial (nondiabetic rats GFR 0.85 +/- 0.07; RPF 2.27 +/- 0.13 ml.min-1.100 g-1). Because diabetic rats with hyperglycemia also had an increased urinary excretion of prostacyclin metabolite 6-keto-prostaglandin F1 alpha (220.6 +/- 62.8 ng/24 h) compared with nondiabetic rats (51.2 +/- 2.7 ng/24 h), we wondered whether excessive prostacyclin formation contributed to hyperfiltration and hyperperfusion in this setting. Indomethacin infusion partially reduced GFR (1.25 +/- 0.07 to 1.06 +/- 0.07 ml.min-1.100 g-1, P less than 0.05) and RPF (2.85 +/- 0.11 to 2.46 +/- 0.12 ml.min-1.100 g-1, P less than 0.01) in diabetic rats. The combined infusion of ANP antiserum and indomethacin normalized GFR and RPF in diabetic rats with hyperglycemia (1.27 +/- 0.05 to 0.88 +/- 0.05 and 2.84 +/- 0.10 to 2.22 +/- 0.06 ml.min-1.100 g-1, respectively; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1992 Apr
PMID:Atrial natriuretic peptide and prostacyclin synergistically mediate hyperfiltration and hyperperfusion of diabetic rats. 153 57

It is generally recognized that formation of a platelet-fibrin-rich thrombus in an atherosclerotic coronary artery is the basis of unstable angina and acute myocardial infarction. Platelet hyperactivity has been identified in coronary risk factors such as hyperlipidemia and diabetes mellitus. Persistent activation of these cells results in release of growth factors that may contribute to the progression of atherosclerosis. Several recent studies show that endothelium, by generating or metabolizing a host of vasoactive substances, plays a critical role in the modulation of vascular tone. Important among these substances are prostacyclin (PGI2) and endothelium-derived relaxing factor (EDRF). The endothelium-dependent modulation of coronary artery tone correlates with the severity of atherosclerosis and the number of coronary risk factors. Procedures such as angioplasty and coronary bypass surgery injure the endothelium. The loss of endothelial smooth muscle relaxant function may contribute to the vasoconstriction and thrombosis often observed soon after these procedures. Thrombolysis (and subsequent reperfusion of the coronary artery) is also associated with severe endothelial dysfunction, with a resulting vasoconstrictor influence on the coronary vascular bed. Activation of leukocytes and their presence in the reperfused myocardium contribute to progression of myocardial injury by release of oxygen free radicals and proteolytic enzymes. Thus, it seems that a perturbation in this delicate equilibrium in cellular interactions relates to genesis and progression of myocardial ischemia.
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PMID:Platelet-leukocyte-endothelial interactions in coronary artery disease. 154 43

We studied serum thromboxane (TXB2), the prostacyclin metabolite, 6-keto-PGF1 (6KPGF1) glucose, insulin, and lipid/lipoprotein profiles in 27 patients with non-insulin-dependent diabetes mellitus (NIDDM) who were switched from therapy with glibenclamide (GLB) (with [GLBH] or without phenformin) to gliclazide for 3 months. We found that therapy with gliclazide was followed by a decrease in serum TXB2 (281.8 +/- 128.3 to 149.1 +/- 77.0 mg/L, P less than .001) and an increase in serum 6KPGF1 (60.5 +/- 19.1 to 96.0 +/- 40.3 mg/L, P less than .001). This was accompanied by a decrease in total and low-density lipoprotein (LDL) cholesterol and an increase in high-density lipoprotein (HDL) cholesterol, within the HDL3 cholesterol fraction. These changes were seen despite the fact that neither fasting plasma glucose nor insulin changed with therapy. These findings suggest that gliclazide may have beneficial actions on cardiovascular risk factors in these NIDDM patients.
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PMID:Thromboxane/prostacyclin balance in type II diabetes: gliclazide effects. 157 13

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.
Diabetes Res Clin Pract 1992 May
PMID:Partial purification of serum prostacyclin stimulatory activity by heparin-agarose column; abnormality detected in diabetics. 160 Aug 48

This paper attempts to provide a short review of the evidence for: 1. Increased platelet production of thromboxane A2 and reduced vascular production of prostacyclin in the human and also animal models of diabetes. 2. Reduced depressor responsiveness to arachidonic acid of anaesthetized alloxan- and streptozotocin-induced diabetic rats. 3. Enhanced constrictor responsiveness to arachidonic acid in blood-perfused hindquarters of alloxan-induced diabetic rats. 4. Potentiation by the thromboxane A2-mimetic, U46619, of constrictor responses to 5-hydroxytryptamine in Krebs'-perfused hindquarters and kidneys of both control and alloxan-induced diabetic rats. 5. Alterations during diabetes in production of, and responsiveness to, eicosanoids may contribute to the cardiovascular changes which occur in this disease.
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PMID:Cardiovascular sensitivity changes to eicosanoids in rats with experimentally induced diabetes mellitus. 162 40

PGE2 is a potent antilipolytic agent produced by adipose tissue, but its role as a physiological regulator of triglyceride lipolysis is controversial because inhibitors of prostaglandin synthesis have not enhanced hormone-stimulated lipolysis in adipose tissue consistently. Adipose tissue also produces PGI2, but this eicosanoid has not had a demonstrated effect on lipolysis under physiological conditions previously. We investigated both PGE2 and PGI2 production and their effects on lipolysis in rat adipose tissue. We found that 1) EPI-stimulated PGE2 production (like PGI2 production) requires the cooperation of adipocytes and endothelial cells, 2) adipose tissue produces PGE2 and PGI2 at comparable rates, 3) indomethacin inhibits EPI-induced PGE2 and PGI2 production and has no effect on EPI-stimulated lipolysis when added to a mixture of adipocytes and endothelial cells or to intact epididymal fat pads, 4) PGI2 is a potent lipolytic agent when added to isolated adipocytes in the absence of endothelial cells under physiological conditions, 5) the magnitudes and the ED50s of the antilipolytic effect of PGE2 and the lipolytic effect of PGI2 in isolated adipocytes in the absence of endothelial cells are comparable, 6) PGI2 antagonizes the antilipolytic effect of PGE2 in isolated adipocytes in the absence of endothelial cells in a dosage-related manner, and 7) the antilipolytic effect of added PGE2 in isolated adipocytes is greater in the absence of endothelial cells than in their presence, suggesting that endogenous eicosanoid production reduces the effectiveness of added PGE2. These studies demonstrate that catecholamine-induced lipolysis is under the coordinate control of PGE2, a potent antilipolytic agent, and PGI2, a potent lipolytic agent.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1992 Aug
PMID:Coordinate control of lipolysis by prostaglandin E2 and prostacyclin in rat adipose tissue. 162 67

1. In addition to metabolic and neurohumoral factors endothelium-derived autacoids like the nitric oxide radical NO and prostacyclin are effective regulators of vascular tone and thus tissue perfusion. NO is produced in endothelial cells from L-arginine by a Ca2+/calmodulin-dependent enzyme NO synthase. In addition, the NO radical is ultimately cleaved from all nitrovasodilators and resembles their vasoactive and antiaggregatory principle, which is used under pathological conditions as substitution therapy for impaired endothelial function and autacoid production. Impaired endothelium-dependent vasomotor control has been documented in hypercholesterolaemia, atheromatosis, diabetes, hypertension, and in reperfusion damage. L-arginine supplementation is effective in a few instances.
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PMID:Clinical relevance of endothelium-derived relaxing factor (EDRF). 163 78

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

The efficacy of iloprost, a stable prostacyclin analog, was investigated in a placebo-controlled trial in 109 diabetics with ischemic lesions. 56 patients were randomly allocated to iloprost and 53 patients to placebo. Iloprost was intravenously applied for 6 hours daily on 28 consecutive days at an individually tolerated dose up to 2 ng/kg/min. The control group received identical solvent volumes. In addition all patients had an intensive basic, mainly local, therapy. At the end of the treatment in the iloprost group 31 of 50 patients (62%) showed partial (greater than 30%) or total healing of the lesion(s). In the placebo group this was the case in 12 of 51 patients (22.5%). The difference of 38.5% was statistically significant (p less than 0.05, chi 2-test, alpha = 0.05, beta = 0.1). The percentage of patients who were free of pain increased from 23% to 42% (+19%) in the iloprost group and from 38% to 48% (+10%) in the placebo group. After dose-titration iloprost was well tolerated. Flush, headache and abdominal complaints were the most frequent side effects. Heart rate and blood pressure were not influenced and the control of diabetes was not altered.
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PMID:[Iloprost in the treatment of ischemic tissue lesions in diabetics. Results of a placebo-controlled multicenter study with a stable prostacyclin derivative]. 169 72

Iloprost, a stable prostacyclin analog, was evaluated clinically for its ability to ameliorate the symptoms of peripheral neuropathy associated with diabetes. In an open, nonrandomized trial, 13 diabetic patients with neuropathy but without proliferative retinopathy received an intravenous infusion of Iloprost at a dose of 10 micrograms, at a rate of 0.1 micrograms/kg/h, twice daily for two weeks. The administration of Iloprost relieved the majority of such subjective symptoms as pain, numbness or sensation of cold and to a lesser extent, such autonomic symptoms as dizziness. In contrast, there was little evidence of objective improvement, e.g., in motor nerve conduction velocity. Iloprost treatment significantly inhibited the platelet aggregation rate stimulated by collagen in vitro. In the one patient tested, thermography revealed an increase in skin temperature by more than 2 degrees C. Side effects associated with Iloprost included headache (3 patients) or aggravation of pain in the extremities (2 patients) and could be ameliorated by slowing the infusion rate or by discontinuing the drug (one patient). Iloprost appears to be safe and effective for relieving the symptoms of diabetic neuropathy. Our results provide the rationale for a double-blind, clinical trial in larger populations of diabetics with peripheral neuropathy.
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PMID:Clinical efficacy of a stable prostacyclin analog, iloprost, in diabetic neuropathy. 170 9


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