Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1980 Feb;65(2):496–505. doi: 10.1172/JCI109693

Effect of glucose, independent of changes in insulin and glucagon secretion, on alanine metabolism in the conscious dog.

G I Shulman, W W Lacy, J E Liljenquist, U Keller, P E Williams, A D Cherrington
PMCID: PMC371388  PMID: 7356691

Abstract

To study the effects of hyperglycemia on the metabolism of alanine and lactate independent of changes in plasma insulin and glucagon, glucose was infused into five 36-h-fasted dogs along with somatostatin and constant replacement amounts of both insulin and glucagon. Hepatic uptakes of alanine and lactate were calculated using the arteriovenous difference technique. [14C]Alanine was infused to measure the conversion of alanine and lactate into glucose. Hyperglycemia (delta 115 mg/dl) of 2 h duration caused the plasma alanine level to increase by over 50%. This change was caused by an increase in the inflow of alanine into plasma since the net hepatic uptake of the amino acid did not change. Taken together, the above findings indicate that glucose per se can significantly impair the fractional extraction of alanine by the liver. Hepatic extraction of lactate was also affected by hyperglycemia and had fallen to zero within 90 min of starting the glucose infusion. This fall was associated with a doubling of arterial lactate level. Conversion of [14C]-alanine and [14C]lactate into [14C]glucose was suppressed by 60 +/- 11% after 2 h of hyperglycemia, and because this fall could not be entirely accounted for by decreased lactate extraction an inhibitory effect of glucose on gluconeogenesis within the liver is suggested. These studies indicate that the plasma glucose level per se can be an important determinant of the level of alanine and lactate in plasma as well as the rate at which they are converted to glucose.

Full text

PDF
496

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aguilar-Parada E., Eisentraut A. M., Unger R. H. Pancreatic glucagon secretion in normal and diabetic subjects. Am J Med Sci. 1969 Jun;257(6):415–419. doi: 10.1097/00000441-196906000-00008. [DOI] [PubMed] [Google Scholar]
  2. Baños G., Daniel P. M., Moorhouse S. R., Pratt O. E. The requirements of the brain for some amino acids. J Physiol. 1975 Apr;246(3):539–548. doi: 10.1113/jphysiol.1975.sp010903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chang T. W., Goldberg A. L. The origin of alanine produced in skeletal muscle. J Biol Chem. 1978 May 25;253(10):3677–3684. [PubMed] [Google Scholar]
  4. Cherrington A. D., Lacy W. W., Chiasson J. L. Effect of glucagon on glucose production during insulin deficiency in the dog. J Clin Invest. 1978 Sep;62(3):664–677. doi: 10.1172/JCI109174. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chiasson J. L., Atkinson R. L., Cherrington A. D., Keller U., Sinclair-Smith B. C., Lacy W. W., Liljenquist J. E. Effects of fasting on gluconeogenesis from alanine in nondiabetic man. Diabetes. 1979 Jan;28(1):56–60. doi: 10.2337/diab.28.1.56. [DOI] [PubMed] [Google Scholar]
  6. Chiasson J. L., Liljenquist J. E., Finger F. E., Lacy W. W. Differential sensitivity of glycogenolysis and gluconeogenesis to insulin infusions in dogs. Diabetes. 1976 Apr;25(4):283–291. doi: 10.2337/diab.25.4.283. [DOI] [PubMed] [Google Scholar]
  7. Chochinov R. H., Bowen H. F., Moorhouse J. A. Circulating alanine disposal in diabetes mellitus. Diabetes. 1978 Apr;27(4):420–426. doi: 10.2337/diab.27.4.420. [DOI] [PubMed] [Google Scholar]
  8. Chochinov R. H., Perlman K., Moorhouse J. A. Circulating alanine production and disposal in healthy subjects. Diabetes. 1978 Mar;27(3):287–295. doi: 10.2337/diab.27.3.287. [DOI] [PubMed] [Google Scholar]
  9. Donner D. B., Nakayama K., Lutz U., Sonenberg M. The effects of bioregulators upon amino acid transport and protein synthesis in isolated rat hepatocytes. Biochim Biophys Acta. 1978 Feb 21;507(2):322–336. doi: 10.1016/0005-2736(78)90426-1. [DOI] [PubMed] [Google Scholar]
  10. Fehlmann M., Le Cam A., Kitabgi P., Rey J. F., Freychet P. Regulation of amino acid transport in the liver. Emergence of a high affinity transport system in isolated hepatocytes from fasting rats. J Biol Chem. 1979 Jan 25;254(2):401–407. [PubMed] [Google Scholar]
  11. Felig P., Pozefsky T., Marliss E., Cahill G. F., Jr Alanine: key role in gluconeogenesis. Science. 1970 Feb 13;167(3920):1003–1004. doi: 10.1126/science.167.3920.1003. [DOI] [PubMed] [Google Scholar]
  12. Felig P., Wahren J., Hendler R., Brundin T. Splanchnic glucose and amino acid metabolism in obesity. J Clin Invest. 1974 Feb;53(2):582–590. doi: 10.1172/JCI107593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Felig P., Wahren J. Influence of endogenous insulin secretion on splanchnic glucose and amino acid metabolism in man. J Clin Invest. 1971 Aug;50(8):1702–1711. doi: 10.1172/JCI106659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Fitzpatrick G. F., Meguid M. M., O'Connell R. C., O'Connor N. E., Ball M. R., Brennan M. F. Nitrogen sparing by carbohydrate in man: Intermittent or continuous enteral compared with continuous parenteral glucose. Surgery. 1975 Jul;78(1):105–113. [PubMed] [Google Scholar]
  16. Garber A. J., Karl I. E., Kipnis D. M. Alanine and glutamine synthesis and release from skeletal muscle. I. Glycolysis and amino acid release. J Biol Chem. 1976 Feb 10;251(3):826–835. [PubMed] [Google Scholar]
  17. Goldstein L., Newsholme E. A. The formation of alanine from amino acids in diaphragm muscle of the rat. Biochem J. 1976 Feb 15;154(2):555–558. doi: 10.1042/bj1540555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Herrera M. G., Kamm D., Ruderman N., Cahill Non-hormonal factors in the control of gluconeogenesis. Adv Enzyme Regul. 1966;4:225–235. doi: 10.1016/0065-2571(66)90017-3. [DOI] [PubMed] [Google Scholar]
  19. Jennings A. S., Cherrington A. D., Liljenquist J. E., Keller U., Lacy W. W., Chiasson J. L. The roles of insulin and glucagon in the regulation of gluconeogenesis in the postabsorptive dog. Diabetes. 1977 Sep;26(9):847–856. doi: 10.2337/diab.26.9.847. [DOI] [PubMed] [Google Scholar]
  20. Joseph S. K., Bradford N. M., McGivan J. D. Characteristics of the transport of alanine, serine and glutamine across the plasma membrane of isolated rat liver cells. Biochem J. 1978 Dec 15;176(3):827–836. doi: 10.1042/bj1760827. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Keller U., Cherrington A. D., Liljenquist J. E. Ketone body turnover and net hepatic ketone production in fasted and diabetic dogs. Am J Physiol. 1978 Aug;235(2):E238–E247. doi: 10.1152/ajpendo.1978.235.2.E238. [DOI] [PubMed] [Google Scholar]
  22. Kelley D. S., Potter V. R. Regulation of amino acid transport systems by amino acid depletion and supplementation in monolayer cultures of rat hepatocytes. J Biol Chem. 1978 Dec 25;253(24):9009–9017. [PubMed] [Google Scholar]
  23. Kreisberg R. A., Siegal A. M., Owen W. C. Alanine and gluconeogenesis in man: effect of ethanol. J Clin Endocrinol Metab. 1972 May;34(5):876–883. doi: 10.1210/jcem-34-5-876. [DOI] [PubMed] [Google Scholar]
  24. Mallette L. E., Exton J. H., Park Effects of glucagon on amino acid transport and utilization in the perfused rat liver. J Biol Chem. 1969 Oct 25;244(20):5724–5728. [PubMed] [Google Scholar]
  25. Moreno F. J., Sánchez-Urrutia L., Medina J. M., Sánchez-Medina F., Mayor F. Stimulation of phosphoenolpyruvate carboxykinase (guanosine triphosphate) activity by low concentrations of circulating glucose in perfused rat liver. Biochem J. 1975 Jul;150(1):51–58. doi: 10.1042/bj1500051. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. O'Connell R. C., Morgan A. P., Aoki T. T., Ball M. R., Moore F. D. Nitrogen conservation in starvation: graded responses to intravenous glucose. J Clin Endocrinol Metab. 1974 Sep;39(3):555–563. doi: 10.1210/jcem-39-3-555. [DOI] [PubMed] [Google Scholar]
  27. OWEN E. E., ROBINSON R. R. Amino acid extraction and ammonia metabolism by the human kidney during the prolonged administration of ammonium chloride. J Clin Invest. 1963 Feb;42:263–276. doi: 10.1172/JCI104713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Ruderman N. B., Berger M. The formation of glutamine and alanine in skeletal muscle. J Biol Chem. 1974 Sep 10;249(17):5500–5506. [PubMed] [Google Scholar]
  29. Ruderman N. B., Herrera M. G. Glucose regulation of hepatic gluconeogenesis. Am J Physiol. 1968 Jun;214(6):1346–1351. doi: 10.1152/ajplegacy.1968.214.6.1346. [DOI] [PubMed] [Google Scholar]
  30. Shulman G. I., Liljenquist J. E., Williams P. E., Lacy W. W., Cherrington A. D. Glucose disposal during insulinopenia in somatostatin-treated dogs. The roles of glucose and glucagon. J Clin Invest. 1978 Aug;62(2):487–491. doi: 10.1172/JCI109150. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Wahren J., Felig P. Renal substrate exchange in human diabetes mellitus. Diabetes. 1975 Aug;24(8):730–734. doi: 10.2337/diab.24.8.730. [DOI] [PubMed] [Google Scholar]
  32. Waterhouse C., Keilson J. The contribution of glucose to alanine metabolism in man. J Lab Clin Med. 1978 Nov;92(5):803–812. [PubMed] [Google Scholar]
  33. Wise J. K., Hendler R., Felig P. Influence of glucocorticoids on glucagon secretion and plasma amino acid concentrations in man. J Clin Invest. 1973 Nov;52(11):2774–2782. doi: 10.1172/JCI107473. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES