Kidney International (1984) 25, 869–873; doi:10.1038/ki.1984.103
Dissociation of gluconeogenesis from fluid and phosphate reabsorption in isolated rabbit proximal tubules
Norimoto Yanagawa1, Glenn T Nagami1, Ok Jo1, Jiro Uemasu1 and Kiyoshi Kurokawa1
1Nephrology Divisions, Medical and Research Services, Veterans Administration Sepulveda and Wadsworth Hospitals, and Department of Medicine, the University of California at Los Angeles School of Medicine, Los Angeles, California
Correspondence: Dr N Yanagawa, Nephrology Division, Sepulveda Veterans Administration Medical Center, 16111 Plummer Street, Sepulveda, California 91343, USA
Received 16 March 1983; Revised 2 November 1983.
Top of pageAbstract
Dissociation of gluconeogenesis from fluid and phosphate reabsorption in isolated rabbit proximal tubules. Gluconeogenesis in the kidney is a metabolic function characteristic of proximal tubules. Recent studies suggest that renal gluconeogenesis (GNG) may in some way be coupled to fluid and phosphate reabsorption in the proximal tubule. Therefore, the present studies examined more directly the relationship between GNG and transport of fluid and phosphate using isolated proximal straight tubules of rabbit kidney. Glucose production rates were determined in isolated tubules with a glucose microassay while both phosphate (Jp) and net fluid fluxes (Jv) were measured by the in vitro isolated tubule perfusion technique. Glucose production rates from individual substrates, including pyruvate, lactate, glutamate and
-ketoglutarate, differed significantly, but neither Jv nor Jp was altered when different substrates in the bath medium were used. Inhibition of GNG by 3-mercaptopicolinate did not alter the Jv or Jp. Acid pH (7.0) stimulated GNG and suppressed both Jv and Jp. The addition of 3-mercaptopicolinate at acid pH abolished the stimulatory effect of acid pH on GNG but had no effect on Jv or Jp. These data thus indicate that, in the isolated rabbit renal proximal tubule, GNG rates can be dissociated from both the Jv and Jp and suggest that renal GNG may not directly regulate the fluid and phosphate transport rates in the proximal straight tubule.
Dissociation entre la glucogénèse et la réabsorption de fluides et de phosphates dans des tubules proximaux isolés de lapins. La gluconéogénèse dans le rein est une fonction métabolique caractéristique des tubules proximaux. Des études récentes suggérent que la gluconéogénèse rénale (GNG) pourrait d'une façon ou d'une autre être complée à la réabsorption de fluides et de phosphates dans le tubule proximal. C'est pourquoi ces travaux ont examiné plus directement la relation entre la GNG et le transport de phosphates et de fluides en utilisant des tubules proximaux droits isolés de rein de lapin. Les taux de production de glucose ont été déterminés dans les tubules isolés avec un microdosage du glucose tandis que les flux nets de liquide (Jv) et de phosphates (Jp) étaient mesurés par la technique de perfusion in vitro de tubules isolés. Les taux de production de glucose à partir de substrats individuels, notamment pyruvate, lactate, glutamate et
-cétoglutarate, différaient significativement, mais ni Jv ni Jp n'étaient altérés lorsque ces différents substrats étaient utilisés dans le bain d'incubation. L'inhibition de GNG par du 3-mercaptopicolinate n'a pas altéré Jv ou Jp. Un pH acide (7,0) a stimulé GNG, et supprimé Jv et Jp. L'addition de 3-mercaptopicolinate à un pH acide a abolit l'effet stimulateur du pH acide sur GNG, mais n'a pas eu d'effet sur Jv ou Jp. Ces données indiquent donc que dans le tubule proximal isolé de rein de lapin, les taux de GNG peuvent être dissociés de Jv et de Jp et suggèrent que la GNG rénale pourrait ne pas réguler directement les vitesses de transport de fluides et de phosphates dans le tubule droit proximal.
Top of pageReferences
- Schmidt U, Guder WG: Sites of enzyme activity along the nephron. Kidney Int 9:233–242, 1976
- Malaque A, Endou H, Koseki C, Sakai F: Nephron heterogeneity: Gluconeogenesis from pyruvate in rabbit nephron. FEBS Lett 226:254–256, 1980
- Vandewalle A, Wirthensohn G, Heidrich H, Guder WG: Distribution of hexokinase and phosphoenolypyruvate carboxykinase along the rabbit nephron. Am J Physiol 240:F492–F500, 1981
- Klein KL, Wang MS, Torikai S, Davidson WD, Kurokawa K: Substrate oxidation by isolated single nephron segments of the rat. Kidney Int 20:29–35, 1981
- Cohen J, Kamm DE: Renal metabolism: relation to renal function, in The Kidney (2nd ed), edited by Brenner BM, Rector FC, Jr, Philadelphia, W. B. Saunders and Company, 1981, p 144
- Kida K, Nakajo S, Kamiya F, Toyama Y, Nishio T, Nakagawa H: Renal net glucose release in vivo and its contribution to blood glucose in rats. J Clin Invest 62:721–726, 1978 | ISI | ChemPort |
- Kempson SA, Colon-Otero R, Ou SYL, Turner ST, Dousa TP: Possible role of nicotinamide adenine dinucleotide as an intracellular regulator of renal transport of phosphate in the rat. J Clin Invest 67:1347–1360, 1981 | PubMed |
- Silva P, Hallac R, Spokes K, Epstein FH: Relationship among gluconeogenesis, QO and Na+ transport in the perfused rat kidney. Am J Physiol 242:F508–F513, 1982 | PubMed | ISI | ChemPort |
- Silva P, Ross B, Spokes K: Competition between sodium reabsorption and gluconeogenesis in kidneys of steroid-treated rats. Am J Physiol 238:F290–F295 1980
- Chick W, Like AA: Ultramicro method of determination of glycogen and glucose by enzymic labeling with adenosine triphosphate-r-32P. Anal Biochem 32:340–347, 1969
- Yanagawa N, Nissenson RA, Edwards B, Yeung P, Trizna W, Fine LG: Functional profile of the isolated uremic nephrons. Intrinsic adaptation of phosphate transport in the rabbit proximal tubule. Kidney Int 23:674–683, 1983
- Ross B, Silva P, Bullock S: Role of the malate-aspartate shuttle in renal sodium transport in the rat. Clin Sci 60:419–426, 1981
- Gullans SR, Brazy PC, Dennis VW, Mandel LJ: Interaction between gluconeogenesis and sodium transport in the proximal tubule. Kidney Int (abstract). 23:223, 1983
- Tenenhouse HS, Chu YL: Hydrolysis of nicotinamide-adenine dinucleotide by purified renal brush-border membranes. Biochem J 204:635–638, 1982
- Angielski S, Zielkiewicz J, Dzierzko G: Metabolism of NAD by isolated rat renal brush border membranes. Pfluegers Arch 395:159–161, 1982
- Lang RP, Yanagawa N, Nord E, Sakhrani L, Lee SH, Fine LG: Nucleotide inhibition of phosphate transport in the renal proximal tubules. Am J Physiol 245:F263–F271, 1983
- Baines AD, Ross BD: Redox potential and gluconeogenesis as regulators of phosphate reabsorption in perfused rat kidneys (abstract). Kidney Int 21:250, 1982
- Grahn MF, Butterworth PJ: Modulation of phosphate accumulation in isolated chick kidney cells by gluconeogenic substrates. Biosc Reports 2:661–666, 1982