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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated whether the glomerular synthesis of prostaglandins modulates the glomerular filtration rate and urinary albumin excretion in incipient diabetic nephropathy (defined as urinary albumin excretion between 30 and 300 mg/24 h (microalbuminuria) in two out of three sterile ketone-free 24-h urine collections in patients having insulin-dependent diabetes mellitus (IDDM) without hypertension or other kidney disease). The urinary excretion of prostaglandin E2 was significantly elevated in 8 insulin-dependent diabetic patients with incipient nephropathy as compared with 9 normoalbuminuric IDDM patients and 11 healthy controls: 317 (182-1273); 95 (67-225); 132 (54-263) pg/min, respectively (2p less than 0.01). Glomerular filtration rate (single bolus 51Cr-EDTA technique) and albuminuria (radioimmunoassay) were measured twice within 2 weeks in 8 females having IDDM with incipient nephropathy. The study design was a randomized double-blind trial with the patients receiving either indomethacin (150 mg/day) or placebo for 3 days prior to the kidney function studies. Indomethacin treatment induced a significant reduction in urinary prostaglandin E2 excretion (73%) (2p less than 0.01), urinary albumin excretion rate diminished from 207 (63-253) to 87 (49-147) mg/24 h (2p less than 0.01), fractional clearance of albumin declined (70%) (2p less than 0.01). Glomerular filtration rate remained stable (108 (88-133) versus 110 (95-142) ml/min). Blood glucose and blood pressure were comparable during the placebo and indomethacin treatment (12.6 +/- 3 versus 13.4 +/- 5 mmol/l and 122/79 +/- 3/9 versus 122/82 +/- 4/10 mmHg, respectively). Our results suggest that enhanced glomerular synthesis of vasodilating prostaglandins may accelerate microalbuminuria in incipient diabetic nephropathy.
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PMID:Elevated urinary prostaglandin excretion and the effect of indomethacin on renal function in incipient diabetic nephropathy. 296 80

We investigated whether the glomerular synthesis of prostaglandins modulates the glomerular filtration rate and albuminuria in diabetic nephropathy. The urinary excretion of immunoreactive prostaglandin E2 (253 pg/min) was significantly elevated in eight Type 1 (insulin-dependent) diabetic women with nephropathy as compared with nine normoalbuminuric Type 1 diabetic women (95 pg/min) and 11 non-diabetic women (132 pg/min), respectively (p less than 0.01). Glomerular filtration rate (single bolus 51Cr-EDTA technique) and albuminuria (radioimmunoassay) were measured twice within two weeks in the eight Type 1 diabetic women with nephropathy. All eight patients were on a diabetic diet without sodium restriction. The study was performed as a randomized double-blind trial, with the patients receiving either indomethacin (150 mg/day) or placebo for three days prior to the kidney function studies. Indomethacin treatment induced a significant reduction in urinary prostaglandin E2 excretion (73%, p less than 0.01), glomerular filtration rate diminished from 120 +/- 18 to 106 +/- 17 ml/min/1.73 m2 (p less than 0.05), albuminuria declined from 148 to 69 micrograms/min (median and range) (p less than 0.05) and fractional clearance of albumin diminished 42% (p less than 0.05). Blood glucose concentrations were comparable during the placebo and indomethacin treatment, 13.4 +/- 4 versus 14.2 +/- 3 mmol/l, respectively. Our results suggest that glomerular filtration rate in early diabetic nephropathy is dependent on the enhanced glomerular synthesis of vasodilating prostaglandins.
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PMID:Effects of indomethacin on kidney function in type 1 (insulin-dependent) diabetic patients with nephropathy. 347 10

Abnormal glucose handling in the proximal tubule may play an important role in the development of diabetic nephropathy. Thus, the present study was designed to examine the effect of high glucose on alpha-methyl-D-glucopyranoside (alpha-MG) uptake and its signaling pathways in the primary cultured rabbit renal proximal tubule cells (PTCs). When PTCs were preincubated with 25 or 50 mM glucose for 4 h, 25 or 50 mM glucose significantly inhibited alpha-MG uptake, while 25 or 50 mM mannitol and L-glucose did not affect. Actinomycin D and cycloheximide did not block the effect of high glucose on alpha-MG uptake. Twenty-five millimoles glucose-induced inhibition of alpha-MG uptake was blocked by mepacrine and AACOCF(3), phospholipase A(2) (PLA(2)) inhibitors. Twenty-five millimoles of glucose, not mannitol or L-glucose, significantly increased the [(3)H]-arachidonic acid (AA) release compared to control. In addition, the 25 mM glucose-induced [(3)H]-AA release was completely blocked by mepacrine or AACOCF(3). Indomethacin, a cyclooxygenase inhibitor, blocked the high glucose-induced inhibition of alpha-MG uptake, although econazole, cytochrome P-450 a epoxygenase inhibitor, and nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor, did not. On the other hand, staurosporine and bisindolylmaleimide I, protein kinase C (PKC) inhibitors, blocked 25 mM glucose-induced increase of [(3)H]-AA release and inhibition of alpha-MG uptake. However, neomycin, U 73122, and phospholipase c(PLC) inhibitors did not block the effect of 25 mM glucose on [(3)H]-AA release and alpha-MG uptake. Pretreatment of methoxyverapamil, an L-type Ca(2+) channel blocker, abolished 25 mM glucose-induced increase of [(3)H]-AA release. Indeed, 25 mM glucose increased translocation of cPLA(2) from cytosolic fraction to membrane fraction. In conclusion, the present results demonstrate that high glucose inhibits alpha-MG uptake by the increase of AA release via the activation of PKC.
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PMID:High glucose-induced inhibition of alpha-methyl-D-glucopyranoside uptake is mediated by protein kinase C-dependent activation of arachidonic acid release in primary cultured rabbit renal proximal tubule cells. 1079 10

Endothelin-1 (ET-1) plays an important role in the pathogenic mechanism of diabetic nephropathy. However, the regulatory effects of ET-1 on superoxide and prostaglandin E2 (PGE2) in diabetic glomeruli are unclear. The aim of this study was to determine whether ET-1 exerts a differential effect on the production of superoxide and PGE2 in diabetic glomeruli. The regulatory effects of indomethacin, insulin, dexamethasone, and heparin were also investigated. Freshly isolated glomeruli were obtained from normal and streptozotocin-induced diabetic rats for 1 week (DM1W), 1 month (DM1M), and 3 months (DM3M), respectively. Our results showed that the basal superoxide production of isolated glomeruli was significantly higher in DM1M and DM3M than in the normal rats (p < 0.01). ET-1 stimulated superoxide production in normal, DM1W and DM1M glomeruli (p < 0.01) but not in DM3M rats. The basal production of PGE2 in isolated glomeruli did not differ between diabetic and normal rats. ET-1 also stimulated PGE2 production in diabetic rats (p < 0.05). Pretreatment with indomethacin further enhanced ET-1-stimulated superoxide production in all groups of diabetic rats (p < 0.05), while the ET-1-stimulated PGE2 production was attenuated by indomethacin. Insulin, dexamethasone and heparin had no additional effects on ET-1-mediated superoxide and PGE2 production. In conclusion, basal glomerular production of superoxide but not PGE2 was increased in the diabetic glomeruli. ET-1 further stimulated production of both superoxide and PGE2. Indomethacin could enhance ET-1-stimulated superoxide production while attenuating PGE2 production.
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PMID:Endothelin-1 enhances superoxide and prostaglandin E2 production of isolated diabetic glomeruli. 2063 37

Diabetic nephropathy is associated with increased risk of cardiovascular disease. B-type natriuretic peptide (BNP) plays an important role in cardiovascular pathophysiology and therapeutics. The aim of the present study was to investigate the influence of experimental diabetes on the mechanisms that regulate the relaxant response of the rabbit renal artery to BNP. Arterial relaxations to BNP were enhanced in diabetic rabbits. Indomethacin enhanced BNP-induced relaxation in control rabbits but showed no effect in diabetic rabbits. BNP-induced release of thromboxane A2 or prostacyclin was not different in both groups of animals. Iberiotoxin had no effect on relaxations to BNP in both groups of animals. Charybdotoxin displaced to the right the concentration-response curve to BNP in both group of animals, and inhibited BNP-induced relaxation only in diabetic rabbits. Glibenclamide did not modify the BNP-induced relaxations in control rabbits, but inhibited it in diabetic rabbits. These results suggest that diabetes induces hypereactivity of the rabbit renal artery to BNP by mechanisms that at least include (1) a reduced vasoconstrictor influence of arachidonic acid metabolites via cyclooxygenase 2, which is not related with changes in thromboxane A2 and prostacyclin release from the arterial wall and (2) a selectively increased modulatory activity of KATP and endothelial IKCa channels.
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PMID:Diabetes modifies the role of prostanoids and potassium channels which regulate the hypereactivity of the rabbit renal artery to BNP. 2946 70