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

Renal hypertrophy occurs early in the natural history of human and experimental diabetes and may be a manifestation of the same pathophysiological process which ultimately results in diabetic nephropathy. The precise biological events which stimulate and regulate this growth process remain incompletely understood. We postulated that renal eicosanoids contribute to the development of renal hypertrophy in diabetes. We elected to test the effects of suppression of dienoic eicosanoid metabolism (arachidonic acid metabolism) on renal hypertrophy in diabetic rats by feeding fish oil. Diabetic rats fed fish oil had markedly reduced insulin requirements compared to control rats pair-fed a beef tallow-rich diet. The concentrations of prostaglandin E2, 6-keto-prostaglandin F1 alpha, and thromboxane B2 were depressed in the renal cortex of diabetic rats fed fish oil. This alteration in eicosanoid metabolism was associated with a substantial enhancement of diabetic renal hypertrophy. These results indicate that dietary fish oil has profound effects on renal eicosanoid metabolism in experimental diabetes and that these autocoids may participate in the biological events which regulate diabetic renal hypertrophy.
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PMID:Dietary fish oil enhances renal hypertrophy in experimental diabetes. 170 49

Studies of nondiabetic renal disease suggest that thromboxane may be an important mediator of abnormal renal function. The role of thromboxane in diabetic nephropathy is not fully understood. We measured in a double-blind, randomized, placebo-controlled crossover study the effect of a thromboxane synthase inhibitor (FCE 22178, 400 mg two or three times per day) on urinary excretion of thromboxane B2 and 6-keto-prostaglandin F1 alpha, glomerular filtration rate (measured as clearance of polyfructosan), effective renal plasma flow (clearance of para-aminohippuric acid), fractional clearances of albumin and immunoglobin G and the reabsorption rate of beta 2-microglobulin in 15 patients with type 1 (insulin-dependent) diabetic nephropathy. In seven additional patients, the effect of the thromboxane synthase inhibitor given as 400 mg twice per day was compared with that of the thromboxane synthase inhibitor given as 400 mg three times per day. FCE 22178 administration caused a significant inhibition in the excretion of urinary thromboxane B2 and 2,3-dinor-thromboxane B2 compared with placebo (12.3 +/- 2.1 vs 24.6 +/- 5.1 ng/gm creatinine, p = 0.006, and 78.5 +/- 20.3 vs 335.5 +/- 84.1 ng/gm creatinine, p = 0.004, respectively) without any compensatory increase of 6-keto- prostaglandin F1 alpha or 2,3-dinor-6-keto-prostaglandin F1 alpha that reflect prostacyclin I2 biosynthesis. Glomerular filtration rate, effective renal plasma flow, renal vascular resistance, and filtration fraction were not significantly different after placebo or thromboxane synthase inhibitor treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of selective inhibition of thromboxane synthesis on renal function in diabetic nephropathy. 844 89

Altered functions of mesangial cells (MCs) induced by high glucose levels are thought to play an important role in the pathogenesis of diabetic nephropathy. We investigate whether D-alpha-tocopherol (Toc), an antioxidant, can prevent malfunction of cultured human MCs induced by high-glucose media. Incubating MCs with 33 mmol/L glucose caused increased lipid peroxide (LPO) levels, disturbed cell replication, enhanced cytotoxicity, enhanced activity of the diacylglycerol (DAG)-protein kinase C (PKC) pathway, and overproduction of fibronectin and eicosanoids (6-keto prostaglandin F1 alpha [PGF1 alpha] and thromboxane B2 [TXB2]). The amount of LPO in MCs grown in 5 mmol/L glucose was reduced by the addition of Toc in a dose-dependent manner. Since the maximum effect of Toc on decreasing LPO was achieved at a concentration of 100 mumol/L, this dose was selected for the following experiments. Addition of Toc prevented increased LPO levels and [51Cr]-release from MCs induced by high-glucose media without affecting cell number. Toc decreased the total DAG level and PKC activity in membrane fractions in MCs cultured at both 5 and 33 mmol/L glucose. Furthermore, glucose-induced overproduction of fibronectin and eicosanoids from MCs was completely abolished by Toc. These results strongly suggest that Toc ameliorates glucose-induced malfunctions of MCs in vitro.
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PMID:Protective effect of D-alpha-tocopherol on the function of human mesangial cells exposed to high glucose concentrations. 922 31