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)

Renal clear cell tubules and clear/acidophilic cell tumors were induced in male Sprague-Dawley rats by 7 weeks oral administration (stop model) of N-nitrosomorpholine (NNM) at a concentration of 12 mg/100 ml in the drinking water. Twelve, 23 and 34 weeks after withdrawal of NNM serial cryostat sections of the kidneys were histochemically analyzed for the following parameters: glucose transporter proteins (GLUT1, GLUT2), glycogen content and the activities of glycogen synthase (SYN), glycogen phosphorylase (PHO), glucose-6-phosphatase (G6Pase), glucose-6-phosphate dehydrogenase (G6PDH), hexokinase (HK), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate kinase (PK), succinate dehydrogenase (SDH), malate dehydrogenase (MDH), alkaline phosphatase (ALP), acid phosphatase (ACP) and gamma-glutamyltransferase (GGT). Clear cell (glycogenotic) tubules first appeared at 23 weeks, and clear/acidophilic cell tumors at 34 weeks after withdrawal of the carcinogen. G6Pase, ALP, GGT and GLUT2 were absent in clear cell tubules, clear/acidophilic cell tubules, and clear/acidophilic cell tumors indicating a sequential origin of all these types of lesions from the collecting duct system, in line with previous morphological findings. In comparison to the collecting duct epithelium, glycogenotic tubules demonstrated an increased activity of PHO and reduced activities of glycolytic and mitochondrial enzymes, which were accompanied by a strongly reduced expression of GLUT1. Moderately increased activities of glycolytic and mitochondrial enzymes were observed in the clear cells of clear/acidophilic cell tubules and tumors compared with those in glycogenotic tubules. They had slightly increased activities of the glycolytic enzymes GAPDH and PK compared with normal collecting duct epithelium, while most of them were nearly lacking in GLUT1. Our findings suggest that glycogen storage is not due to an increased uptake of glucose from the blood, but results from a disturbance in intracellular flux of metabolites. The development of clear cell tubules from the normal collecting duct epithelium is accompanied by a markedly decreased expression of GLUT1 along with a reduction in glycolytic and mitochondrial enzymes. This reduction of enzyme activities is replaced by an increase in enzyme activities in clear/acidophilic cell tumors indicating a fundamental shift in carbohydrate metabolism during progression from preneoplastic to neoplastic lesions.
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PMID:Sequential changes in glycogen content, expression of glucose transporters and enzymic patterns during development of clear/acidophilic cell tumors in rat kidney. 147 41

Glucose is actively taken up from the glomerular filtrate into the tubule cells by the Na(+)-dependent active glucose transporter (GT), and passively crosses the basolateral membrane via facilitated diffusion GT. With the use of antibodies directed against two types of GTs, we show the immunocytochemical localization of the Na(+)-dependent active GT (SGLT1) and the erythrocyte/HepG2-type facilitated diffusion GT (GLUT1). For light microscopic observation, frozen sections were stained by the rhodamine labeling method. Counterstaining with fluorescein-phalloidin and 4,6-diamidino-2-phenylindole dihydrochloride (DAPI) was employed to facilitate cell type identification. Immunogold staining was carried out on ultra-thin frozen sections for electron microscopy. The antibody to SGLT1 reacted with a 77 KD protein in immunoblotting of a kidney lysate. By immunocytochemistry, SGLT1 was localized in the microvillous plasma membrane in the apical brush borders of the cells of all three proximal tubule segments (S1, S2, and S3). The antibodies to GLUT1, a member of the facilitated diffusion GT family, were raised against human erythrocyte GT or synthetic oligopeptides derived from HepG2 GT, which reacted with a 48 KD protein in immunoblotting of the kidney lysate. GLUT1 was found at the basolateral plasma membranes of S3 proximal tubule cells, cells of the thick limb of Henle's loop, and collecting duct cells. Combined with known physiological data, our findings suggest that SGLT1 in the apical plasma membrane of the proximal tubule cells is responsible for the Na(+)-dependent active reabsorption of glucose from the glomerular filtrate. GLUT1 in the basolateral plasma membrane of S3 cells may transport reabsorbed glucose to the blood vessels. GLUT1 in the basolateral plasma membranes of cells of the thick limb of Henle's loop and of the collecting duct, on the other hand, may nourish these metabolically active cells by facilitating the diffusion of extracellular glucose provided from blood through the basolateral side of the cells.
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PMID:Localization of Na(+)-dependent active type and erythrocyte/HepG2-type glucose transporters in rat kidney: immunofluorescence and immunogold study. 199 28

Renal oncocytomas, which have previously been shown to originate from the collecting duct system, were induced in male Sprague-Dawley rats by oral administration of N-nitrosomorpholine (NNM) for 7 weeks. The expression of glucose transporter isoforms GLUT1 and GLUT2, and of several enzymes involved in glucose metabolism [hexokinase (HK), pyruvate kinase (PK), lactate dehydrogenase (LDH), malate dehydrogenase (MDH)] were studied by cytochemical approaches in serial cryostat sections of the kidney 12, 23 and 34 weeks after withdrawal of NNM. Oncocytic tubules connected with collecting ducts were first observed 23 weeks, and oncocytomas 34 weeks after withdrawal. The cytochemical pattern of oncocytic tubules and oncocytomas was similar, but differed markedly from that of normal collecting ducts in nearly all variables studied; expression of GLUT1 and hexokinase I proteins were strongly increased; activities of HK, PK and MDH were elevated, while LDH activity was reduced. These results suggest that oncocytic transformation is associated with fundamental changes in energy metabolism which differ from those in cell lineages leading to other types of renal cell tumours, such as clear/acidophilic and basophilic cell tumours. The characteristic over-expression of GLUT1 may be used as a diagnostic criterion for the discrimination between oncocytes and acidophilic (granular) cells in clear/acidophilic renal cell tumours which show a reduced expression of this glucose transporter protein.
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PMID:Over-expression of glucose transporter isoform GLUT1 and hexokinase I in rat renal oncocytic tubules and oncocytomas. 792 15

Glucagon is known to affect glomerular filtration rate and renal tubular solute and fluid transport, although it is only thought to act directly on the thick ascending limb (TAL) and collecting duct (CD). Indeed, previous studies have detected glucagon-sensitive adenylate cyclase exclusively in these nephron segments, suggesting the presence of glucagon receptors. In the present study, we have demonstrated for the first time that glucagon receptor mRNA is expressed in the rat proximal tubule, as well as in the TAL and CD. By autoradiography, we have also shown that specific binding of glucagon occurs in both the renal cortex and medulla. In addition, using proximal tubule brush-border membrane (BBM) vesicles for studies of glucose transport, we have established that glucagon stimulates glucose uptake via a facilitative GLUT-mediated transport process (by 58%; P < 0.005), whereas cAMP stimulates only the sodium glucose-linked transporter ('SGLT')-mediated glucose uptake (by 53%; P < 0.05). Taken together, these findings suggest that glucagon could have a role in controlling proximal tubular transport function, including glucose reabsorption, but unlike in the TAL and CD, the proximal tubule glucagon receptor might not be coupled primarily to adenylate cyclase.
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PMID:Detection of glucagon receptor mRNA in the rat proximal tubule: potential role for glucagon in the control of renal glucose transport. 1260 82

Renal cell carcinomas (RCC) can be subclassified for general purposes into clear cell, papillary cell, chromophobe cell carcinomas and oncocytomas. Other tumours such as collecting duct, medullary, mucinous tubular and spindle cell and associated with Xp 11.2 translocations/TFE 3 gene fusion, are much less common. There is also a residual group of unclassified cases. Previous studies have shown that RCC has high glycolytic rates, and expresses GLUT transporters, but no distinction has been made among the different subtypes of renal cell tumours and their grades of malignancy. In clear renal cell carcinoma (cRCC) glycogen levels increase, glycolysis is activated and gluconeogenesis is reduced. The clear cell subtype of RCC is characterized histologically by a distinctive pale, glassy cytoplasm and this appearance of cRCC is due to abnormalities in carbohydrate and lipid metabolism, and this abnormality results in glycogen and sterol storage. Several isoforms of glucose carriers (GLUTs) have been identified. We show here in a panel of 80 cRCC samples a significant correlation between isoform 5 (GLUT5) and many pathological parameters such as grade of differentiation, pelvis invasion and breaking capsule. GLUT5 expression also appears to associate more strongly with the clear cell RCC subtype. These data suggest a role for the GLUT5 isoform in fructose uptake that takes place in cRCC cells and which subsequently leads to the malignant RCC progression.
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PMID:Fructose transporter GLUT5 expression in clear renal cell carcinoma. 2116 69