Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Streptozotocin diabetes induces a 4-fold increase in the maximal velocity of inner medullary aldose reductase as determined in vitro but increases sorbitol synthesis in intact inner medullary collecting duct (IMCD) cells only 1.3-fold. In order to resolve this discrepancy we investigated the importance of intracellular factors in controlling the role of cellular sorbitol synthesis. These factors include glucose concentration, sorbitol concentration, the activity of the NADPH-regenerating pentose phosphate pathway, intracellular NADP and NADPH content, and intracellular reduced (GSH) and oxidized glutathione (GSSG). It was found that the apparent Km of cellular sorbitol production for glucose was identical in control and diabetic rats (56 +/- 18 vs. 59 +/- 14 mmol/l D-glucose), whereas Vmax increased by 31% in diabetes. In inner medullary collecting duct cells of diabetic rats containing 146 +/- 5 mumol sorbitol/g protein, sorbitol synthesis was slightly lower (-15%), compared to cells which had been sorbitol-depleted prior to the experiment (87 +/- 4 mumol sorbitol/g protein). However, no inhibitory effect of sorbitol (up to 200 mmol/l) was observed on aldose reductase activity in vitro. In diabetic rats the content of NADPH was about 32% lower than in the control rats (3.8 +/- 0.3 vs. 5.6 +/- 0.4 mumol/g protein) and the ratio of NADPH/NADP was decreased from 25.6 +/- 5.1 to 8.6 +/- 1.7. In homogenates of the inner medulla the activity of 6-phospho-gluconate dehydrogenase (EC 1.1.1.43) was identical in both experimental groups, so the pentose phosphate shunt seems to be unaltered. GSH content in diabetic rats was also diminished (4.02 +/- 0.67 mumol/g protein vs. 7.41 +/- 0.5 mumol/g protein) and the GSH/GSSG ratio fell from 92.6 to 57.4. In enzyme tests in vitro an apparent Km of 7.3 +/- 1.9 mumol/l of the aldose reductase for NADPH was found; NADP acted as competitive inhibitor with an apparent K(i) of 183 +/- 31 mumol/l. Aldose reductase activity was also found to be strongly inhibited by the SH-group reagent p-chloromercurybenzoesulfonate (apparent K(i) = 0.85 x 10(-6) mol/l). Combining the results obtained on the properties of the aldose reductase in vitro and the observation made in the intact cells, the investigators suggest that the decrease in NADPH/NADP ratio, as well as changes in the redox state in the cells of diabetic animals, can play a significant role in the control of sorbitol synthesis.
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PMID:Control of sorbitol metabolism in renal inner medulla of diabetic rats: regulation by substrate, cosubstrate and products of the aldose reductase reaction. 824 Dec 88

Pathological accumulations of glycogen were studied in the kidney tubular epithelium in untreated STZ-induced diabetic rats of 50 days diabetes duration. Blood glucose concentrations were approximately 17 mM, and the animals had no ketonuria. At the termination of the experiment, the kidneys were perfusion-fixed, and serial sections were cut from the renal capsule to the tip of the papilla and stained with toluidine blue and periodic acid Schiff. By tracing tubular profiles from section to section in a light microscope, the outlines of nephrons were reconstructed, and abnormal glycogen accumulations were mapped in accordance with the outlines. The exact segmental localization, character, and extension of the glycogen accumulations were determined. The predominant location of the pathological glycogen accumulations was in the thick ascending limb of Henle's loop. Dot-shaped and diffuse-appearing glycogen accumulations were discretely distributed throughout the segment, and large confluent cytoplasmic accumulations of glycogen were also present. On a continuous basis, glycogen was present only in the cortical thick ascending limb of Henle's loop and the macula densa segment excluding the macula densa cells. In the distal convoluted tubule and the cortical collecting duct system, scattered dot-shaped and diffuse glycogen accumulations were discretely distributed. Furthermore, glycogen appeared as confluent, cytoplasmic accumulations in the initial part of the descending thin limb of Henle's loop. In addition, glycogen accumulations were found in nuclei within a narrow stripe of the outer stripe of the outer medulla in the medullary thick ascending limb of Henle's loop.
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PMID:Structure and segmental localization of glycogen in the diabetic rat kidney. 849 12

Experiments were performed to evaluate the hypothesis that the early stage of Type 1 diabetes mellitus (DM) increases renal angiotensin II (AngII) concentration and angiotensin type 1 (AT) receptor protein levels. Nineteen or twenty days after vehicle (Sham rats) or streptozotocin (STZ rats) treatment, plasma [AngII] was higher in STZ rats (152 +/- 23 fmol/ml) than in Sham rats (101 +/- 7 fmol/ml); however, kidney [AngII] did not differ between groups. AT1 receptor protein expression was greater in STZ kidneys than in Sham kidneys. This increase was restricted to the cortex, where AT1 protein levels were elevated by 77 +/- 26% (42 kDa) and 101 +/- 16% (58 kDa) in STZ kidneys. Immunohistochemistry revealed this effect to be most evident in distal nephron segments including the connecting tubule/cortical collecting duct. Increased renal cortical AT1 receptor protein and circulating AngII levels are consistent with an exaggerated AngII-dependent influence on renal function during the early stage of DM in the rat.
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PMID:Renal AT1 receptor protein expression during the early stage of diabetes mellitus. 1199 Dec 2

In current study, the effect of angiotensin receptor blocker Micardis on the localization and expression of aquaporin-2 (AQP2) was investigated in the renal medullary collecting duct of mice with diabetic nephropathy (DN). Mice were divided into three groups: normal group, DN group and Micardis-treated group. Six weeks after establishment of STZ-induced DN model in mice, the expression of AQP2 in renal medulla was detected measured by semiquantitative immunofluorescence histochemistry and Western blot techniques, and the localization of AQP2 by confocal immunofluorescence laser scanning microscopy. The results showed that the urinary osmolality was decreased in DN group as compared with normal group (2.39+/-0.11 vs 3.16+/-0.16, P<0.05). Although the localization of AQP2 on the renal medulla was unchanged, the expression of AQP2 was increased significantly in DN group as compared with normal group. Micardis could partly attenuate above changes. It was concluded that treatment with Micardis could partly rectify the abnormal expression of AQP2 in renal medulla of DN mice, which suggested that rennin-angiotensin system (RAS) is implicated in the pathogenesis of DN by regulating the expression of AQP2.
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PMID:Effect of Micardis on the expression of renal medulla aquaporin-2 in diabetic mice. 1856 21

NADPH oxidase 4 (NOX4) is the most abundant NOX isoform in the kidney; however, its importance for renal function has only recently emerged. The NOX4-dependent pathway regulates many factors essential for proper sodium handling in the distal nephron. However, the functional significance of this pathway in the control of sodium reabsorption during the initiation of chronic kidney disease is not established. The goal of this study was to test Nox4-dependent ENaC regulation in two models: SS hypertension and STZ-induced type 1 diabetes. First, we showed that genetic ablation of Nox4 in Dahl salt-sensitive (SS) rat attenuated a high-salt (HS)-induced increase in epithelial Na+ channel (ENaC) activity in the cortical collecting duct. We also found that H2 O2 upregulated ENaC activity, and H2 O2 production was reduced in both the renal cortex and medulla in SSNox4-/- rats fed an HS diet. Second, in the streptozotocin model of hyperglycemia-induced renal injury ENaC activity in hyperglycemic animals was elevated in SS but not SSNox4-/- rats. NaCl cotransporter (NCC) expression was increased compared to healthy controls, while expression values between SS and SSNox4-/- groups were similar. These data emphasize a critical contribution of the NOX4-mediated pathway in maladaptive upregulation of ENaC-mediated sodium reabsorption in the distal nephron in the conditions of HS- and hyperglycemia-induced kidney injury.
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PMID:NOX4-dependent regulation of ENaC in hypertension and diabetic kidney disease. 3279 94