Background: Potassium (K+) input occurs after meals or during ischemic exercise and is accompanied by a high concentration of L-lactate in plasma (PL-lactate). Methods: We examined whether infusing 100 µmol L-lactic acid/min for 15 min would lead to a fall in the arterial plasma K+ concentration (PK). We also aimed to evaluate the mechanisms involved in normal rats compared with rats with acute hyperkalemia caused by a shift of K+ from cells or a positive K+ balance. Results: There was a significant fall in PK in normal rats (0.25 mM) and a larger fall in PK in both models of acute hyperkalemia (0.6 mM) when the PL-lactate rose. The arterial PK increased by 0.8 mM (p < 0.05) 7 min after stopping this infusion despite a 2-fold rise in the concentration of insulin in arterial plasma (PInsulin). There was a significant uptake of K+ by the liver, but not by skeletal muscle. In rats pretreated with somatostatin, PInsulin was low and infusing L-lactic acid failed to lower the PK. Conclusions: A rise in the PL-lactate in portal venous blood led to a fall in the PK and insulin was permissive. Absorption of glucose by the Na+-linked glucose transporter permits enterocytes to produce enough ADP to augment aerobic glycolysis, raising the PL-lactate in the portal vein to prevent postprandial hyperkalemia.

1.
Wasserman K, Stringer WW, Casaburi R, Zhang Y-Y: Mechanism of the exercise hyperkalemia: an alternate hypothesis. J Appl Physiol 1997;83:631–643.
2.
Steele A, deVeber H, Quaggin SE, Scheich A, Ethier J, Halperin ML: What is responsible for the diurnal variation in potassium excretion? Am J Physiol 1994;267:R554–R560.
3.
Clausen T: Regulation of active Na+-K+ transport in skeletal muscle. Physiol Rev 1986;66:542–580.
4.
Ellis RJ, Pinheiro TJT: Danger – misfolding proteins. Nature 2002;416:483–484.
5.
Counillon LL, Pouyssegur RJ: The members of the Na+/H+ exchanger gene family: their structure, function, expression, and regulation; in Seldin DW, Giebisch G (ed): The Kidney: Physiology & Pathophysiology. Philadelphia, Lippincott Williams & Wilkins, 2000, pp 223–234.
6.
Ewart HS, Klip A: Hormonal regulation of the Na+-K+-ATPase: mechanisms underlying rapid and sustained changes in pump activity. Am J Physiol 1995;269:C295–C311.
7.
Clausen T, Flatman JA: The effect of catecholamines on Na-K transport and membrane potential in rat soleus muscle. J Physiol 1977;270:383–424.
8.
Stanley WC, Gertz EW, Wisneski JA, Neese RA, Morris DL, Brooks GA: Lactate extraction during net lactate release in legs of humans during exercise. J Appl Physiol 1986;60:1116–1120.
9.
Watford M, Lund P, Krebs HA: The utilization of glucose and the production of lactate in vitro preparations of rat small intestine: effect of vascular perfusion. Biochem J 1979;178:589–596.
10.
McGarry JD, Kuwajima M, Newgard CB, Foster DW: From dietary glucose to liver glycogen: the full circle round. Annu Rev Nutr 1987;7:51–73.
11.
Hanson PJ, Parsons DS: Isolation and metabolic characteristics of rat and chicken enterocytes. J Physiol 1976;255:775–795.
12.
Kamel KS, Wei C: Controversial issues in treatment of hyperkalemia. Nephrol Dialysis Transpl 2003;18:2215–2218.
13.
Halperin ML, Vinay P, Gougoux A, Pichette C, Jungas RL: Regulation of the maximum rate of renal ammoniagenesis in the acidotic dog. Am J Physiol 1985;248:F607–F615.
14.
Jungas RL: Best literature values for the pK of carbonic and phosphoric acid under physiologic conditions. Anal Biochem 2006;349:1–15.
15.
Goguen JM, Cheema-Dhadli S, Halperin ML: Can insulin cause metabolic acidosis? Clin Invest Med 1992;15:A29.
16.
Juel C, Halestrap AP: Lactate transport in skeletal muscle – role and regulation of the monocarboxylate transporter. J Physiol 1999;517:633–642.
17.
Gowrishankar M, Kamel KS, Halperin ML: A brain protein-centered view of H+ buffering. J Am Soc Nephrol 2007;18:2278–2280.
18.
Vasuvattakul S, Warner LC, Halperin ML: Quantitative role of the intracellular bicarbonate buffer system in response to an acute acid load. Am J Physiol 1992;262:R305–R309.
19.
Corbic M, Lebrec D, Le Dafniet M, Erlinger S: A new method to measure portal and hepatic blood flow using taurocholate in the rat. Hepatology 1984;4:112–115.
20.
Kowalski TJ, Wu G, Watford M: Rat adipose tissue amino acid metabolism in vivo as assessed by microdialysis and arteriovenous techniques. Am J Physiol 1997;273:E613–E622.
21.
Lin SH, Lin YF, Cheema-Dhadli S, Davids MR, Halperin ML: Hypercalcaemia and metabolic alkalosis with betel nut chewing: emphasis on its integrative pathophysiology. Nephrol Dial Transplant 2002;17:708–714.
22.
Halperin ML, Rolleston FS: Clinical Detective Stories: A Problem-Based Approach to Clinical Cases in Energy and Acid-Base Metabolism, ed 1. London, Portland Press, 1993.
23.
Crane R: Intestinal absorption of sugars. Physiol Rev 1960;40:789–825.
24.
Kellett GL, Brot-Laroche E, Mace OJ, Leturque A: Sugar absorption in the intestine: the role of GLUT2. Annu Rev Nutr 2008;28:35–54.
25.
Jungas RL: Lectures on Gastrointestinal Physiology and the Hormonal Regulation of Energy Metabolism. Farmington, University of Connecticut Health Center, 2002.
26.
Carlisle EJF, Donnelly SM, Ethier J, Quaggin SE, Kaiser U, Vasuvattakul S, et al: Modulation of the secretion of potassium by accompanying anions in humans. Kidney Int 1991;39:1206–1212.
27.
Halperin ML, Kamel KS: Dynamic interactions between integrative physiology and molecular medicine: the key to understand the mechanism of action of aldosterone in the kidney. Can J Physiol Pharmacol 2000;78:587–594.
28.
Lin P, Cheema-Dhadli S, Chayaraks S, Chen CB, Gowrishankar M, Halperin ML: Physiological role of the potential alkali load in the diet of the rat for acid-base balance. Am J Physiol 1998;274:F1037–F1044.
29.
Cheema-Dhadli S, Chong CK, Lin SH, Kamel KS, Halperin ML: Control of potassium excretion, a Paleolithic approach. Curr Opin Nephrol Hypertens 2006;15:430–436.
30.
Kamel KS, Halperin ML: Intrarenal urea recycling leads to a higher rate of renal excretion of potassium: a hypothesis with clinical implications. Curr Opin Nephrol Hypertens 2011;20:547–554.
31.
Ho K: A critically swift response: insulin-stimulated potassium and glucose transport in skeletal muscle. Clin J Am Soc Nephrol 2011;6:1513–1516.
32.
Halperin ML, Cheema-Dhadli S, Haynes FJ, Yip CC: A theoretical analysis of the turnover of the hepatic insulin receptor in the rat. Clin Invest Med 1986;9:141–143.
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