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

The effects of hypoxia on prostanoid production were studied in atria from normal, acute diabetic and insulin-treated diabetic rats. Diabetes was induced by intravenous administration of 65 mg/kg of streptozotocin, the rats were killed 5 days later. Hypoxia was performed by incubation of the atria during 60 min in nitrogen-equilibrated glucose free Krebs' solution followed by 15 min of reoxygenation. The prostanoids 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha) and thromboxane B2 (TXB2), stable metabolites of prostacyclin and TXA2, respectively, as well as PGF2, were measured by reversed phase HPLC-UV. In control atria, the production of 6-keto PGF1 alpha was equivalent to that of PGE2, whereas TXB2 was released in a much smaller amount. In diabetic atria, 6-keto PGF1 alpha production was reduced by 65%, whereas TXB2 release was increased by 158% compared to the controls. When the normal atria were exposed to 60 min of hypoxia, the release of 6-keto PGF1 alpha increased by 142% compared to basal values and remained elevated after 15 min of reoxygenation whereas in diabetic and insulin-treated diabetic tissues the 6-keto PGF1 alpha production was not modified by the hypoxia-reoxygenation period. The release of TXB2 was increased after 60 min hypoxia in normal as well as in diabetic and insulin-treated diabetic tissues and remained elevated during the reoxygenation. The PGE2 output increased only after the onset of the reoxygenation in the three groups studied.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prostanoid production in hypoxic rat isolated atria: influence of acute diabetes. 784 89

Previous studies in experimental diabetes have demonstrated cardiovascular abnormalities of the beta-adrenergic system and reduced adrenergically stimulated renal renin secretion. To examine the defect in the beta-adrenergic signal, glomerular cyclic adenosine monophosphate (cAMP) levels were measured in response to isoproterenol and other humoral agonists (coincubated with the phosphodiesterase inhibitor isomethylxanthine) in nondiabetic and diabetic BB/Wor rats. Basal (unstimulated) levels of glomerular cAMP did not differ between control and diabetic BB/Wor rats, nor did cAMP accumulation differ on incubation with the humoral agonists PGE2 and histamine. However, on incubation with varied concentrations of the nonselective beta-adrenergic agonist isoproterenol, control glomeruli demonstrated a twofold increase in cAMP while a negligible response was observed in diabetic glomeruli. Peak levels of cAMP were higher in control (192 +/- 24 pmol/mg protein) than in diabetic (141 +/- 8 pmol/mg protein) glomeruli (p < 0.01). No differences were observed on incubation with the adenylate cyclase stimulator forskolin. Measurement of glomerular beta-adrenoreceptors by coincubation with iodine 125-labeled cyanopindolol demonstrated no differences in either receptor number (Bmax) or affinity (KD). These data indicate that a specific defect in beta-adrenergic signalling exists in glomerular tissue from spontaneously diabetic rats. Because no decrease in forskolin-stimulated adenylate cyclase was observed, defective coupling of the receptor to its effector, perhaps through the guanine nucleotide stimulatory protein, may account for these observations.
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PMID:Defective glomerular beta-adrenergic signal transmission in spontaneously diabetic rats. 805 89

The present work studies the urinary excretion of PGE2 and PGI2 (6-keto PGF 1 alpha) in 11 insulin-dependent diabetic patients with chronic renal failure with a glomerular filtration rate of 33.9 +/- 9.03 ml/min who had hyporeninaemic hypoaldosteronism to evaluate the influence of these prostaglandins on the appearance of this latter process. The results obtained in this group of patients were compared with those of a control group of healthy individuals, another group of nine non-diabetic patients with CRF, and a last group of eight insulin-dependent diabetic patients with normal renal function to evaluate to what extent the possible variations in prostaglandin excretion could be related to the diabetes, CRF, or a conjunction of both processes. The results of the groups of diabetic patients with CRF were Ccr 33.9 +/- 9.03 ml/min, decreased (P < 0.0001) with respect to the control group and with no difference with the CRF group without diabetes; plasma potassium (4.7 +/- 0.4 mEq/l), increased (P < 0.005) with respect to the values found in the control group; plasma bicarbonate (17.8 +/- 1.8 mEq/l), decreased (P < 0.005) with respect to the control group and also, though not significantly, with respect to the group of non-diabetic patients with CRF. Plasma aldosterone (pg/ml): resting 44.3 +/- 14.9; standing 65.7 +/- 63.5 and post-frusemide 65.5 +/- 58.6, decreased (P < 0.01) with respect to the other three groups. Plasma renin activity (PRA) (ng/ml/h): resting 0.34 +/- 0.3; standing 0.6 +/- 0.4, post-frusemide 0.9 +/- 0.5, decreased significantly with respect to the other three groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Urinary prostaglandins (PGE2 and PGI2) in hyporeninaemic hypoaldosteronism in diabetic patients with chronic renal failure. 805 30

Microalbuminuria is characteristic in diabetic nephropathy and is thought to be influenced by renal hemodynamics, especially by the metabolism of prostaglandins (PGs) in glomruli. To reduce urinary albumin excretion in patients with non-insulin-dependent diabetes mellitus (NIDDM), we administered 100 mg of cilostazol, a phosphodiesterase inhibitor, daily for 3 months. The urinary albumin index (UAI: microgram albumin/mg creatinine) decreased significantly after 3 months of administering cilostazol. Urinary excretions of thromboxane B2 (TXB2), a stable metabolite of thromboxane A2, decreased significantly after treatment. However, it had no effects on urinary excretions of PGE2 and 6-keto PGF1 alpha (6KF), a stable metabolite of prostacyclin. The ratio 6KF/TXB2 has been known to reflect the renal metabolism of PGs. In this study, urinary 6KF/TXB2 ratio increased significantly in parallel with a significant reduction of UAI. Cilostazol had no adverse effects on the control of blood glucose and lipids. In conclusion, cilostazol has a beneficial effect on UAI in patients with NIDDM by reducing renal production of TXB2., which increases 6KF/TXB2 ratio.
Diabetes Res Clin Pract
PMID:Effects of cilostazol, a phosphodiesterase inhibitor, on urinary excretion of albumin and prostaglandins in non-insulin-dependent diabetic patients. 813 17

Diabetes mellitus alters the cellular production of eicosanoids in a number of tissues, including the kidney, and these agents have in turn been implicated in the pathogenesis of diabetic nephropathy. As delineated in the streptozotocin diabetic rat (SDR) model, a preferential enhancement of glomerular synthesis of the vasodilatory prostaglandins (PGs) PGE2 and PGI2 with concurrent smaller increases in thromboxane (TX)A2 occurs within 1 week after induction of diabetes. This early alteration in glomerular synthesis of eicosanoids in the SDR has been linked to glucose-induced activation of the glomerular protein kinase C signalling system that enhances phospholipase A2 activity and, therefore, release of membrane-bound arachidonic acid for oxygenation. The preferential increase in glomerular production of vasodilatory PGs may contribute to the glomerular hyperfiltration that is characteristic of early diabetes. After more prolonged (months) diabetes in the SDR, glomerular generation and urinary excretion of thromboxane (TX) are preferentially enhanced. Studies with selective inhibitors of TX synthesis in the SDR have implicated this eicosanoid in the pathogenesis of both albuminuria and glomerular structural changes (basement membrane thickening and mesangial matrix expansion). Direct stimulation of matrix protein production has been demonstrated in cultured mesangial cells in response to both TX and high ambient concentrations of glucose. The actions of TX and glucose on mesangial cell matrix production appear to be interactive, with each signalled through distinct pathways of protein kinase C activation.
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PMID:Eicosanoids in the pathogenesis of the functional and structural alterations of the kidney in diabetes. 823 21

Changes in glomerular eicosanoid production have been implicated in the development of diabetes-induced glomerular hyperfiltration and glomerular mesangial cells (GMC) are major eicosanoid-producing cells within the glomerulus. However, the mechanism for the effect of diabetes mellitus on glomerular mesangial eicosanoid production is unknown. The present study therefore examined whether elevated glucose concentrations activate protein kinase C (PKC) in GMC and whether this PKC activation mediates an effect of elevated glucose concentrations to increase the release of arachidonic acid and eicosanoid production by GMC. The percentage of [3H]arachidonic acid release per 30 min by preloaded GMC monolayers was significantly increased after 3-h exposure to high glucose (20 mM) medium (177% vs control medium) and this increase was sustained after 24-h exposure to high glucose concentrations. 3-h and 24-h exposure to high glucose medium also increased PGE2, 6-keto-PGF1 alpha, and thromboxane (TXB2) production by GMC. High glucose medium (20 mM) increased PKC activity in GMC at 3 and 24 h (168% vs control). In contrast, osmotic control media containing either L-glucose or mannitol did not increase arachidonic acid release, eicosanoid production, or PKC activity in GMC. Inhibiting glucose-induced PKC activation with either H-7 (50 microM) or staurosporine (1 microM) prevented glucose-induced increases in arachidonic acid release and eicosanoid production by GMC. These data demonstrate that elevated extracellular glucose concentrations directly increase the release of endogenous arachidonic acid and eicosanoids by GMC via mechanisms dependent on glucose-induced PKC activation.
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PMID:Glucose-induced protein kinase C activity regulates arachidonic acid release and eicosanoid production by cultured glomerular mesangial cells. 825 44

Insulin binding and insulin responsiveness are altered by dietary fat-induced changes in the fatty acid composition of the adipocyte plasma membrane. Feeding a high P/S diet increased polyunsaturated fatty acid content of major membrane phospholipids of adipocyte plasma membrane in normal and diabetic animals, increased membrane linoleic acid content, and prevented a decrease in arachidonic acid level in diabetic animals. The high P/S diet increased insulin binding in control animals. Animals fed the high P/S diet had significantly higher rates of insulin-stimulated glucose transport and lipogenesis than did animals fed the low P/S diet. Feeding a high P/S diet significantly increased the amount of glucose transported when expressed as a function of the specific amount of insulin bound. To determine if dietary fat-induced alterations in the fatty acid composition of skeletal muscle lipid alter insulin-dependent and basal muscle metabolism, contralateral epitrochlearis and extensor digitorum longus muscles were isolated and incubated in vitro. High levels of dietary omega-3 fatty acids reduced PGE2 and PGF2 alpha synthesis in extensor digitorum longus and epitrochlearis muscle. Insulin increased glucose and amino acid transport; the increase in glucose transport by insulin was significantly greater after consumption of the high omega-3 fatty acid diet. Rats fed high levels of omega-3 fatty acids showed reduced net protein degradation in the presence and absence of insulin due to decreased rates of protein degradation and synthesis. These experiments indicate that high levels of dietary omega-3 fatty acids alter muscle membrane composition, glucose transport, and metabolism of muscle protein. To determine if dietary fatty acids alter the onset of diabetes and insulin binding to liver nuclei in spontaneously diabetic rats, weanling rats were fed chow or semipurified diets containing 20% (w/w) fat of either high or low P/S ratio. Feeding a high P/S diet increased insulin binding to liver nuclei of control and diabetic animals. Although diet did not alter the onset of diabetes, insulin binding to liver nuclei is higher in animals at the onset of diabetes than in highly diabetic animals. Eight-week-old female C57 B 6J lean and ob/ob mice were fed semipurified diets containing 20% (w/w) fat of either high or low P/S ratio to investigate the effect of diet on specific binding of insulin to liver nuclei. Insulin binding was highest in nuclei from lean mice fed a high P/S diet. Specific binding of insulin to nuclei from obese mice was also increased by the high P/S diet, but to a lesser extent.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dietary lipids influence insulin action. 835 37

The short-term effects of elevated glucose on cyclic GMP (cGMP) and eicosanoid production in pig aortic endothelial cell monolayers was determined by incubating cells in 5.5 mM or 44 mM glucose for 6 hours. Bradykinin- or A23187-stimulated cGMP production was significantly reduced in cells incubated in 44 mM glucose compared with 5.5 mM glucose. Stimulation of cGMP levels with exogenously added nitric oxide (NO) was also decreased to a similar extent in cells exposed to 44 mM glucose. These data suggest that NO production stimulated by bradykinin or A23187 was unchanged by elevated glucose. Assayed eicosanoids, including 6-ketoprostaglandin (PG) F1 alpha, PGE2 alpha, and 15(S)-hydroxy-(5Z, 8Z, 11Z, 13E)-eicosatetraenoic acid, stimulated by bradykinin or A23187, were increased in cells exposed to 44 mM glucose. These eicosanoid products formed from exogenously added arachidonic acid did not differ between cells incubated in 5.5 mM or 44 mM glucose. Hyperosmolar concentrations of mannose or sucrose had no effect on cGMP levels but did mimic the effect of elevated glucose on eicosanoid production. These data suggest that hyperglycemia in diabetes may interfere with NO-induced guanylate cyclase activation but not NO production in the endothelium and that increased phospholipase activity, secondary to hyperosmolarity, may account for elevated eicosanoid levels.
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PMID:Effect of elevated glucose on cyclic GMP and eicosanoids produced by porcine aortic endothelium. 838 14

There is increasing evidence that a link between the polyol pathway and prostaglandins is important in the pathogenesis of diabetic nephropathy. The presence of the polyol pathway in the kidneys of normal animals, the galactose-fed rat, and animals with experimental diabetes has been established. While aldose reductase (AR) immunoreactive protein (AR-IRP) and AR mRNA are expressed at high levels in renal medulla, the sites of AR synthesis and regulation and metabolic consequences of AR activity in renal cortex are uncertain. The present study was conducted to test the hypothesis that AR expression and PGE2 production are coordinately regulated in glomerular mesangial cells. To test this hypothesis, we measured AR-IRP, AR mRNA, and PGE2 production in mesangial cells isolated from rats maintained on diets containing normal chow (MC-N), 50% galactose (MC-G), and 50% dextrin (MC-D). The rank order for each parameter studied (AR-IRP, AR mRNA, PGE2) was MC-N > MC-G > MC-D. Western blot analysis demonstrated that MC-N (optical density [OD] 1.0), MC-G (OD 0.59), and MC-D (OD 0.25) express AR-IRP. Slot-blot analyses demonstrated that levels of AR mRNA were greatest in MC-N (1.0), intermediate in MC-G (0.49), and lowest in MC-D (0.31). Ribonuclease (RNase) protection analyses demonstrated a similar pattern of AR mRNA expression, with MC-N at 1.0, MC-G at 0.60, and MC-D at 0.33. PGE2 production (pg/5 x 10(4) cells/30 min) was highest in MC-N (278 +/- 29), intermediate in MC-G (110 +/- 9), and lowest in MC-D (37 +/- 4).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Aldose reductase expression and prostaglandin E2 production are coordinately regulated in cultured rat mesangial cells. 848 43

The insulin resistance syndrome has been noted as an interesting and important new risk factor for coronary artery disease. The syndrome consists of hypertension, glucose intolerance, and dyslipidemia, all of which are likely to be derived from insulin insensitivity. In subjects with nonobese and nondiabetic essential hypertension, steady-state plasma glucose (SSPG) was higher than in normotensive subjects during an insulin sensitivity test, indicating reduced insulin sensitivity to glucose metabolism in the hypertensive group. SSPG correlated with the percentage decrease of branched chain amino acids, free fatty acids, and serum potassium during the insulin sensitivity test. With a 2-h insulin infusion, serum norepinephrine, epinephrine, plasminogen activator inhibitor 1, and intraplatelet Ca2+ decreased significantly, but 6-keto-prostaglandin (PG) F1 alpha and PGE2 did not change. Insulin resistance decreased by using antihypertensive treatments with bunazosin, cilazapril, amlodipine, and benidipine in hypertensive subjects. Diagnostic criteria for the insulin resistance syndrome, including clinical values for each risk factor, were developed. Lowered insulin sensitivity and hyperinsulinemia were demonstrated in subjects with both vasospastic and coronary artery stenotic angina. The insulin resistance syndrome together with hyperinsulinemia is likely to induce atherosclerotic changes, possibly through reduced rather than excessive action of insulin.
Diabetes 1996 Jul
PMID:Mechanism and clinical implication of insulin resistance syndrome. 867 91


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