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. 1996 Jul 1;98(1):125–135. doi: 10.1172/JCI118756

Effect of prior exercise on the partitioning of an intestinal glucose load between splanchnic bed and skeletal muscle.

K S Hamilton 1, F K Gibbons 1, D P Bracy 1, D B Lacy 1, A D Cherrington 1, D H Wasserman 1
PMCID: PMC507408  PMID: 8690783

Abstract

Exercise leads to marked increases in muscle insulin sensitivity and glucose effectiveness. Oral glucose tolerance immediately after exercise is generally not improved. The hypothesis tested by these experiments is that after exercise the increased muscle glucose uptake during an intestinal glucose load is counterbalanced by an increase in the efficiency with which glucose enters the circulation and that this occurs due to an increase in intestinal glucose absorption or decrease in hepatic glucose disposal. For this purpose, sampling (artery and portal, hepatic, and femoral veins) and infusion (vena cava, duodenum) catheters and Doppler flow probes (portal vein, hepatic artery, external iliac artery) were implanted 17 d before study. Overnightfasted dogs were studied after 150 min of moderate treadmill exercise or an equal duration rest period. Glucose ([14C]glucose labeled) was infused in the duodenum at 8 mg/kg x min for 150 min beginning 30 min after exercise or rest periods. Values, depending on the specific variable, are the mean +/- SE for six to eight dogs. Measurements are from the last 60 min of the intraduodenal glucose infusion. In response to intraduodenal glucose, arterial plasma glucose rose more in exercised (103 +/- 4 to 154 +/- 6 mg/dl) compared with rested (104 +/- 2 to 139 +/- 3 mg/dl) dogs. The greater increase in glucose occurred even though net limb glucose uptake was elevated after exercise (35 +/- 5 vs. 20 +/- 2 mg/min) as net splanchnic glucose output (5.1 +/- 0.8 vs. 2.1 +/- 0.6 mg/kg x min) and systemic appearance of intraduodenal glucose (8.1 +/- 0.6 vs. 6.3 +/- 0.7 mg/kg x min) were also increased due to a higher net gut glucose output (6.1 +/- 0.7 vs. 3.6 +/- 0.9 mg/kg x min). Adaptations at the muscle led to increased net glycogen deposition after exercise [1.4 +/- 0.3 vs. 0.5 +/- 0.1 mg/(gram of tissue x 150 min)], while no such increase in glycogen storage was seen in liver [3.9 +/- 1.0 vs. 4.1 +/- 1.1 mg/(gram of tissue x 150 min) in exercised and sedentary animals, respectively]. These experiments show that the increase in the ability of previously working muscle to store glycogen is not solely a result of changes at the muscle itself, but is also a result of changes in the splanchnic bed that increase the efficiency with which oral glucose is made available in the systemic circulation.

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Selected References

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  1. Ahlborg G., Felig P. Influence of glucose ingestion on fuel-hormone response during prolonged exercise. J Appl Physiol. 1976 Nov;41(5 Pt 1):683–688. doi: 10.1152/jappl.1976.41.5.683. [DOI] [PubMed] [Google Scholar]
  2. Ahlborg G., Felig P. Substrate utilization during prolonged exercise preceded by ingestion of glucose. Am J Physiol. 1977 Sep;233(3):E188–E194. doi: 10.1152/ajpendo.1977.233.3.E188. [DOI] [PubMed] [Google Scholar]
  3. Bogardus C., Thuillez P., Ravussin E., Vasquez B., Narimiga M., Azhar S. Effect of muscle glycogen depletion on in vivo insulin action in man. J Clin Invest. 1983 Nov;72(5):1605–1610. doi: 10.1172/JCI111119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cersosimo E., Judd R. L., Miles J. M. Insulin regulation of renal glucose metabolism in conscious dogs. J Clin Invest. 1994 Jun;93(6):2584–2589. doi: 10.1172/JCI117270. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chan T. M., Exton J. H. A rapid method for the determination of glycogen content and radioactivity in small quantities of tissue or isolated hepatocytes. Anal Biochem. 1976 Mar;71(1):96–105. doi: 10.1016/0003-2697(76)90014-2. [DOI] [PubMed] [Google Scholar]
  6. Cowan J. S., Hetenyi G., Jr Glucoregulatory responses in normal and diabetic dogs recorded by a new tracer method. Metabolism. 1971 Apr;20(4):360–372. doi: 10.1016/0026-0495(71)90098-9. [DOI] [PubMed] [Google Scholar]
  7. DEBODO R. C., STEELE R., ALTSZULER N., DUNN A., BISHOP J. S. ON THE HORMONAL REGULATION OF CARBOHYDRATE METABOLISM; STUDIES WITH C14 GLUCOSE. Recent Prog Horm Res. 1963;19:445–488. [PubMed] [Google Scholar]
  8. Davis M. A., Williams P. E., Cherrington A. D. Effect of a mixed meal on hepatic lactate and gluconeogenic precursor metabolism in dogs. Am J Physiol. 1984 Sep;247(3 Pt 1):E362–E369. doi: 10.1152/ajpendo.1984.247.3.E362. [DOI] [PubMed] [Google Scholar]
  9. Felig P., Wahren J., Hendler R. Influence of oral glucose ingestion on splanchnic glucose and gluconeogenic substrate metabolism in man. Diabetes. 1975 May;24(5):468–475. doi: 10.2337/diab.24.5.468. [DOI] [PubMed] [Google Scholar]
  10. Garetto L. P., Richter E. A., Goodman M. N., Ruderman N. B. Enhanced muscle glucose metabolism after exercise in the rat: the two phases. Am J Physiol. 1984 Jun;246(6 Pt 1):E471–E475. doi: 10.1152/ajpendo.1984.246.6.E471. [DOI] [PubMed] [Google Scholar]
  11. Golden S., Wals P. A., Katz J. An improved procedure for the assay of glycogen synthase and phosphorylase in rat liver homogenates. Anal Biochem. 1977 Feb;77(2):436–445. doi: 10.1016/0003-2697(77)90257-3. [DOI] [PubMed] [Google Scholar]
  12. Greenway C. V., Stark R. D. Hepatic vascular bed. Physiol Rev. 1971 Jan;51(1):23–65. doi: 10.1152/physrev.1971.51.1.23. [DOI] [PubMed] [Google Scholar]
  13. Hartley C. J., Hanley H. G., Lewis R. M., Cole J. S. Synchronized pulsed Doppler blood flow and ultrasonic dimension measurement in conscious dogs. Ultrasound Med Biol. 1978;4(2):99–110. doi: 10.1016/0301-5629(78)90035-2. [DOI] [PubMed] [Google Scholar]
  14. Holloszy J. O., Constable S. H., Young D. A. Activation of glucose transport in muscle by exercise. Diabetes Metab Rev. 1986;1(4):409–423. doi: 10.1002/dmr.5610010405. [DOI] [PubMed] [Google Scholar]
  15. Ivy J. L., Frishberg B. A., Farrell S. W., Miller W. J., Sherman W. M. Effects of elevated and exercise-reduced muscle glycogen levels on insulin sensitivity. J Appl Physiol (1985) 1985 Jul;59(1):154–159. doi: 10.1152/jappl.1985.59.1.154. [DOI] [PubMed] [Google Scholar]
  16. Jackson R. A., Peters N., Advani U., Perry G., Rogers J., Brough W. H., Pilkington T. R. Forearm glucose uptake during the oral glucose tolerance test in normal subjects. Diabetes. 1973 Jun;22(6):442–458. doi: 10.2337/diab.22.6.442. [DOI] [PubMed] [Google Scholar]
  17. James D. E., Burleigh K. M., Kraegen E. W., Chisholm D. J. Effect of acute exercise and prolonged training on insulin response to intravenous glucose in vivo in rat. J Appl Physiol Respir Environ Exerc Physiol. 1983 Dec;55(6):1660–1664. doi: 10.1152/jappl.1983.55.6.1660. [DOI] [PubMed] [Google Scholar]
  18. King D. S., Baldus P. J., Sharp R. L., Kesl L. D., Feltmeyer T. L., Riddle M. S. Time course for exercise-induced alterations in insulin action and glucose tolerance in middle-aged people. J Appl Physiol (1985) 1995 Jan;78(1):17–22. doi: 10.1152/jappl.1995.78.1.17. [DOI] [PubMed] [Google Scholar]
  19. Koivisto V. A., Yki-Järvinen H. Effect of exercise on insulin binding and glucose transport in adipocytes of normal humans. J Appl Physiol (1985) 1987 Oct;63(4):1319–1323. doi: 10.1152/jappl.1987.63.4.1319. [DOI] [PubMed] [Google Scholar]
  20. LeBlanc J., Nadeau A., Richard D., Tremblay A. Studies on the sparing effect of exercise on insulin requirements in human subjects. Metabolism. 1981 Nov;30(11):1119–1124. doi: 10.1016/0026-0495(81)90057-3. [DOI] [PubMed] [Google Scholar]
  21. Lloyd B., Burrin J., Smythe P., Alberti K. G. Enzymic fluorometric continuous-flow assays for blood glucose, lactate, pyruvate, alanine, glycerol, and 3-hydroxybutyrate. Clin Chem. 1978 Oct;24(10):1724–1729. [PubMed] [Google Scholar]
  22. Maehlum S., Felig P., Wahren J. Splanchnic glucose and muscle glycogen metabolism after glucose feeding during postexercise recovery. Am J Physiol. 1978 Sep;235(3):E255–E260. doi: 10.1152/ajpendo.1978.235.3.E255. [DOI] [PubMed] [Google Scholar]
  23. Maehlum S., Hermansen L. Muscle glycogen concentration during recovery after prolonged severe exercise in fasting subjects. Scand J Clin Lab Invest. 1978 Oct;38(6):557–560. doi: 10.1080/00365517809108819. [DOI] [PubMed] [Google Scholar]
  24. McMahon M. M., Schwenk W. F., Haymond M. W., Rizza R. A. Underestimation of glucose turnover measured with [6-3H]- and [6,6-2H]- but not [6-14C]glucose during hyperinsulinemia in humans. Diabetes. 1989 Jan;38(1):97–107. doi: 10.2337/diab.38.1.97. [DOI] [PubMed] [Google Scholar]
  25. Mikines K. J., Sonne B., Farrell P. A., Tronier B., Galbo H. Effect of physical exercise on sensitivity and responsiveness to insulin in humans. Am J Physiol. 1988 Mar;254(3 Pt 1):E248–E259. doi: 10.1152/ajpendo.1988.254.3.E248. [DOI] [PubMed] [Google Scholar]
  26. Moghimzadeh E., Nobin A., Rosengren E. Fluorescence microscopical and chemical characterization of the adrenergic innervation in mammalian liver tissue. Cell Tissue Res. 1983;230(3):605–613. doi: 10.1007/BF00216204. [DOI] [PubMed] [Google Scholar]
  27. Mondon C. E., Dolkas C. B., Reaven G. M. Site of enhanced insulin sensitivity in exercise-trained rats at rest. Am J Physiol. 1980 Sep;239(3):E169–E177. doi: 10.1152/ajpendo.1980.239.3.E169. [DOI] [PubMed] [Google Scholar]
  28. Musch T. I., Friedman D. B., Pitetti K. H., Haidet G. C., Stray-Gundersen J., Mitchell J. H., Ordway G. A. Regional distribution of blood flow of dogs during graded dynamic exercise. J Appl Physiol (1985) 1987 Dec;63(6):2269–2277. doi: 10.1152/jappl.1987.63.6.2269. [DOI] [PubMed] [Google Scholar]
  29. O'Doherty R. M., Bracy D. P., Osawa H., Wasserman D. H., Granner D. K. Rat skeletal muscle hexokinase II mRNA and activity are increased by a single bout of acute exercise. Am J Physiol. 1994 Feb;266(2 Pt 1):E171–E178. doi: 10.1152/ajpendo.1994.266.2.E171. [DOI] [PubMed] [Google Scholar]
  30. Okajima F., Chenoweth M., Rognstad R., Dunn A., Katz J. Metabolism of 3H- and 14C-labelled lactate in starved rats. Biochem J. 1981 Feb 15;194(2):525–540. doi: 10.1042/bj1940525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Pagliassotti M. J., Myers S. R., Moore M. C., Neal D. W., Cherrington A. D. Magnitude of negative arterial-portal glucose gradient alters net hepatic glucose balance in conscious dogs. Diabetes. 1991 Dec;40(12):1659–1668. doi: 10.2337/diab.40.12.1659. [DOI] [PubMed] [Google Scholar]
  32. Pestell R. G., Ward G. M., Galvin P., Best J. D., Alford F. P. Impaired glucose tolerance after endurance exercise is associated with reduced insulin secretion rather than altered insulin sensitivity. Metabolism. 1993 Mar;42(3):277–282. doi: 10.1016/0026-0495(93)90074-x. [DOI] [PubMed] [Google Scholar]
  33. Pruett E. D., Oseid S. Effect of exercise on glucose and insulin response to glucose infusion. Scand J Clin Lab Invest. 1970 Nov;26(3):277–285. doi: 10.3109/00365517009046234. [DOI] [PubMed] [Google Scholar]
  34. Ren J. M., Semenkovich C. F., Gulve E. A., Gao J., Holloszy J. O. Exercise induces rapid increases in GLUT4 expression, glucose transport capacity, and insulin-stimulated glycogen storage in muscle. J Biol Chem. 1994 May 20;269(20):14396–14401. [PubMed] [Google Scholar]
  35. Richter E. A., Garetto L. P., Goodman M. N., Ruderman N. B. Enhanced muscle glucose metabolism after exercise: modulation by local factors. Am J Physiol. 1984 Jun;246(6 Pt 1):E476–E482. doi: 10.1152/ajpendo.1984.246.6.E476. [DOI] [PubMed] [Google Scholar]
  36. Richter E. A., Garetto L. P., Goodman M. N., Ruderman N. B. Muscle glucose metabolism following exercise in the rat: increased sensitivity to insulin. J Clin Invest. 1982 Apr;69(4):785–793. doi: 10.1172/JCI110517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Richter E. A., Mikines K. J., Galbo H., Kiens B. Effect of exercise on insulin action in human skeletal muscle. J Appl Physiol (1985) 1989 Feb;66(2):876–885. doi: 10.1152/jappl.1989.66.2.876. [DOI] [PubMed] [Google Scholar]
  38. Rodnick K. J., Haskell W. L., Swislocki A. L., Foley J. E., Reaven G. M. Improved insulin action in muscle, liver, and adipose tissue in physically trained human subjects. Am J Physiol. 1987 Nov;253(5 Pt 1):E489–E495. doi: 10.1152/ajpendo.1987.253.5.E489. [DOI] [PubMed] [Google Scholar]
  39. Shulman G. I., Lacy W. W., Liljenquist J. E., Keller U., Williams P. E., Cherrington A. D. Effect of glucose, independent of changes in insulin and glucagon secretion, on alanine metabolism in the conscious dog. J Clin Invest. 1980 Feb;65(2):496–505. doi: 10.1172/JCI109693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Sonne B., Galbo H. Carbohydrate metabolism during and after exercise in rats: studies with radioglucose. J Appl Physiol (1985) 1985 Nov;59(5):1627–1639. doi: 10.1152/jappl.1985.59.5.1627. [DOI] [PubMed] [Google Scholar]
  41. Stumvoll M., Chintalapudi U., Perriello G., Welle S., Gutierrez O., Gerich J. Uptake and release of glucose by the human kidney. Postabsorptive rates and responses to epinephrine. J Clin Invest. 1995 Nov;96(5):2528–2533. doi: 10.1172/JCI118314. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Vergauwen L., Hespel P., Richter E. A. Adenosine receptors mediate synergistic stimulation of glucose uptake and transport by insulin and by contractions in rat skeletal muscle. J Clin Invest. 1994 Mar;93(3):974–981. doi: 10.1172/JCI117104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Wasserman D. H., Geer R. J., Rice D. E., Bracy D., Flakoll P. J., Brown L. L., Hill J. O., Abumrad N. N. Interaction of exercise and insulin action in humans. Am J Physiol. 1991 Jan;260(1 Pt 1):E37–E45. doi: 10.1152/ajpendo.1991.260.1.E37. [DOI] [PubMed] [Google Scholar]
  44. Wasserman D. H., Lacy D. B., Bracy D., Williams P. E. Metabolic regulation in peripheral tissues and transition to increased gluconeogenic mode during prolonged exercise. Am J Physiol. 1992 Aug;263(2 Pt 1):E345–E354. doi: 10.1152/ajpendo.1992.263.2.E345. [DOI] [PubMed] [Google Scholar]
  45. Wasserman D. H., Mohr T., Kelly P., Lacy D. B., Bracy D. Impact of insulin deficiency on glucose fluxes and muscle glucose metabolism during exercise. Diabetes. 1992 Oct;41(10):1229–1238. doi: 10.2337/diab.41.10.1229. [DOI] [PubMed] [Google Scholar]
  46. Wasserman D. H. Regulation of glucose fluxes during exercise in the postabsorptive state. Annu Rev Physiol. 1995;57:191–218. doi: 10.1146/annurev.ph.57.030195.001203. [DOI] [PubMed] [Google Scholar]
  47. Wasserman D. H., Williams P. E., Lacy D. B., Green D. R., Cherrington A. D. Importance of intrahepatic mechanisms to gluconeogenesis from alanine during exercise and recovery. Am J Physiol. 1988 Apr;254(4 Pt 1):E518–E525. doi: 10.1152/ajpendo.1988.254.4.E518. [DOI] [PubMed] [Google Scholar]

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