Intra- and inter-nephron heterogeneity of gluconeogenesis in the rat: effects of chronic metabolic acidosis and potassium depletion
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The intra- and inter-nephron heterogeneity of renal gluconeogenesis within rat proximal tubules and the effects of chronic metabolic acidosis and chronic potassium(K)-depletion were studied using isolated proximal tubules of rats by directly measuring glucose synthesized.
The gluconeogenic activity from pyruvate and glutamine in control rats was almost limited to within the early proximal tubule (S1: 45.4±5.7 pmol/mm/60 min from pyruvate; 58.0±6.0 from glutamine). Very low, but detectable gluconeogenesis was observed in the middle portion of the proximal tubule (S2:9.9±2.2 from pyruvate; 4.8±1.1 from glutamine). The rate of glucose production in the terminal proximal tubule (S3) was negligible. Furthermore, gluconeogenesis from glutamine of superficial (SF) nephrons was significantly higher than that of juxtamedullary (JM) ones, whereas no difference was seen in gluconeogenesis from pyruvate.
In acidotic and K-depleted rats, significant increase could be seen in S1 and S2, but the increase in S3 was not significant. By the serial determination in acidosis, the glucose production from both substrates was found to be the highest at the second 1 mm segment from the glomerulus, and it decreased downward along the proximal tubule. In acidosis, glucose production from both substrates in SF nephrons and that from glutamine in JM ones were elevated significantly compared with the control, but that from pyruvate in JM nephrons did not change.
These results suggest that S1 of the SF nephron plays the most important role in gluconeogenesis in the control, whereas S1 of the JM nephron and S2 contribute to gluconeogenesis in acidotic and/or possibly K-depleted rats.
Key wordsRenal gluconeogenesis Chronic metabolic acidosis Potassium depletion Microdissected nephron segment Superficial nephron Juxtamedullary nephron Nephron heterogeneity Substrate specificity
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- Bergmeyer HU, Bernt E, Schmidt F, Stork H (1974)d-Glucose: Determination with hexokinase and glucose-6-phosphate dehydrogenase. In: Bergmeyer HU (ed) Methods of enzymatic analysis, vol 4, (2nd edn). Verlag Chemie, Weinheim, pp 1196–1201Google Scholar
- Burch HB, Narins RG, Chu C, Fagioli S, Choi S, McCarthy W, Lowry OH (1978a) Distribution along the rat nephron of three enzymes of gluconeogenesis in acidosis and starvation. Am J Physiol 235:246–253Google Scholar
- Burch HB, Choi S, McCarthy WZ, Wong PY, Lowry OH (1978b) The location of glutamine synthetase within the rat and rabbit nephron. Biochem Biophys Res Commun 82:498–505Google Scholar
- Cohen J, Kam DE (1981) Renal metabolism: relation to renal function In: Brenner BM, Rector Jr FC (eds) The kidney (2nd edn), vol I. Saunders, Philadelphia, pp 209–213Google Scholar
- Curthoys NP, Lowry OH (1973) The distribution of glutaminase isoenzymes in the various structures of the nephron in normal, acidotic, and alkalotic rat kidney. J Biol Chem 248:162–168Google Scholar
- Dawson AG (1977) Contribution of pH-sensitive metabolic processes to pH homeostasis in isolated rat kidney tubules. Biochim Biophys Acta 499:85–98Google Scholar
- Endou H, Imai M (1982) Introduction to new approaches in renal pharmacology. Adv Pharmacol Ther II 3:287–293Google Scholar
- Endou H, Nonoguchi H, Nakada J, Takehara Y, Yamada H (1985a) Glutamine metabolism in the kidney: ammoniagenesis and gluconeogenesis in isolated nephron segments of rats. In: Dzurik R, Lichardus B, Guder W (eds) Kidney metabolism and function. Martinus Nijhoff Publishers, Dordrecht, pp 26–33Google Scholar
- Endou H, Nonoguchi H, Takehara Y, Yamada H, Nakada J (1985b) Intranephron heterogeneity of ammoniagenesis and gluconeogenesis in rats. Contr Nephrol 47:98–104Google Scholar
- Friedrichs D, Schoner W (1973) Stimulation of renal gluconeogenesis by inhibition of the sodium pump. Biochim Biophys Acta 304:142–160Google Scholar
- Gardner LI, MacLachlan EA, Berman H (1952) Effect of potassium deficiency on carbon dioxide, cation, and phosphate content of muscle. J Gen Physiol 36:153–159Google Scholar
- Good DW, Burg MB (1984) Ammonia production by individual segments of the rat nephron. J Clin Invest 73:602–610Google Scholar
- Goodman AD, Fuisz RE, Cahill Jr GF (1966) Renal gluconeogenesis in acidosis, alkalosis, and potassium deficiency: its possible role in regulation of renal ammonia production. J Clin Invest 45:612–619Google Scholar
- Goorno WE, Rector Jr FC, Seldin DW (1967) Relation of renal gluconeogenesis to ammonia production in the dog and rat. Am J Physiol 213:969–974Google Scholar
- Goto E, Sakakibara F, Nishida T, Kawamura T, Sano T, Tsuchida I, Sakamoto N (1984) Gluconeogenesis and ammonia production in the isolated perfused rat kidney: the effect of starvation, acidosis and diabetic ketosis. Nagoya J Med Sci 46:67–78Google Scholar
- Guder WG, Schmidt U (1974) The localization of gluconeogenesis in rat nephron. (Determination of phosphoenolpyruvate carboxykinase in microdissected tubules). Hoppe-Seyler's Z Physiol Chem 355:273–278Google Scholar
- Guder WG, Schmidt U (1976) Enzymatic organization of carbohydrate metabolism along the nephron. Proc 6th Int Congr Nephrol (Florence, 1975). Karger, Basel, pp 187–195Google Scholar
- Kamm DE, Cahill Jr GF (1969) Effect of acid-base status on renal and hepatic gluconeogenesis in diabetes and fasting. Am J Physiol 216:1207–1212Google Scholar
- Kempson SA, Kowalski JC, Puschett JB (1983) Inhibition of renal brush border phosphate transport and stimulation of renal gluconeogenesis by cyclic AMP and parathyroid hormone. Biochem Pharmacol 32:1533–1537Google Scholar
- Kida K, Nakajo S, Kamiya F, Toyama Y, Nishio T, Nakagawa H (1978) Renal net glucose release in vivo and its contribution to blood glucose in rats. J Clin Invest 62:721–726Google Scholar
- Krebs HA (1964) Gluconeogenesis. Proc R Soc Lond 159:545–564Google Scholar
- Longshaw ID, Alleyne GAO, Pogson CI (1972) The effect of steroids and ammonium chloride acidosis on phosphoenolpyruvate carboxykinase in rat kidney cortex. II. The kinetics of enzyme induction. J Clin Invest 51:2284–2291Google Scholar
- Lowry OH, Passonneau JV, Schulz DW, Rock MK (1961) The measurement of pyridine nucleotides by enzymatic cycling. J Biol Chem 236:2746–2755Google Scholar
- Maleque A, Endou H, Koseki C, Sakai F (1980) Nephron heterogeneity: gluconeogenesis from pyruvate in rabbit nephron. FEBS Letters 116:154–156Google Scholar
- Morel F, Chabardes D, Inbert M (1976) Functional segmentation of rabbit distal tubule by microdetermination of hormone-dependent adenylate cyclase activity. Kidney Int 9:264–277Google Scholar
- Nonoguchi H, Uchida S, Shiigai T, Endou H (1985) Effect of chronic metabolic acidosis on ammonia production froml-glutamine in microdissected rat nephron segments. Pflügers Arch 403:229–235Google Scholar
- Nonoguchi H, Takehara Y, Endou H (1986) Intra- and internephron heterogeneity of ammoniagenesis in rats: Effects of chronic metabolic acidosis and potassium depletion. Pflügers Arch (in press)Google Scholar
- Schmidt U, Dubach UC (1971) Quantitative Histochemie am Nephron. Prog Histochem Cytochem 2:185–298Google Scholar
- Silva P, Hallac R, Spokes K, Epstein FH (1982) Relationship among gluconeogenesis, Qo2, and Na+ transport in the perfused rat kidney. Am J Physiol 242:F508-F513Google Scholar
- Takehara Y, Nonoguchi H, Endou H (1986) Roles of phosphate-dependent and independent glutaminase I in intranephron ammoniagenesis in rats. Pflügers Arch (submitted)Google Scholar
- Vandewalle A, Wirthensohn G, Heidrich H, Guder WG (1981) Distribution of hexokinase and phosphoenolpyruvate carboxykinase along the rabbit nephron. Am J Physiol 240:F492-F500Google Scholar
- Wang MS, Kurokawa K (1984) Renal gluconeogenesis: axial and internephron heterogeneity and the effect of parathyroid hormone. Am J Physiol 246:F59-F66Google Scholar
- Wilson AF, Simmons DH (1970) Relationships between potassium, chloride, intracellular and extracellular pH in dogs. Clin Sci 39:731–745Google Scholar