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. 1969 Mar;48(3):574–583. doi: 10.1172/JCI106016

Liver and kidney metabolism during prolonged starvation

Oliver E Owen 1,2,3,4,5, Philip Felig 1,2,3,4,5, Alfred P Morgan 1,2,3,4,5, John Wahren 1,2,3,4,5, George F Cahill Jr 1,2,3,4,5
PMCID: PMC535723  PMID: 5773093

Abstract

This study quantifies the concentrations of circulating insulin, growth hormone, glucose, free fatty acids, glycerol, β-hydroxybutyrate, acetoacetate, and alpha amino nitrogen in 11 obese subjects during prolonged starvation. The sites and estimated rates of gluconeogenesis and ketogenesis after 5-6 wk of fasting were investigated in five of the subjects.

Blood glucose and insulin concentrations fell acutely during the 1st 3 days of fasting, and alpha amino nitrogen after 17 days. The concentration of free fatty acids, β-hydroxybutyrate, and acetoacetate did not reach a plateau until after 17 days.

Estimated glucose production at 5-6 wk of starvation is reduced to approximately 86 g/24 hr. Of this amount the liver contributes about one-half and the kidney the remainder. Approximately all of the lactate, pyruvate, glycerol, and amino acid carbons which are removed by liver and kidney are converted into glucose, as evidenced by substrate balances across these organs.

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Selected References

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

  1. BEARN A. G., BILLING B. H., SHERLOCK S. Hepatic glucose output and hepatic insulin sensitivity in diabetes mellitus. Lancet. 1951 Oct 20;2(6686):698–701. doi: 10.1016/s0140-6736(51)91476-6. [DOI] [PubMed] [Google Scholar]
  2. BORCHGREVINK C. F., HAVEL R. J. TRANSPORT OF GLYCEROL IN HUMAN BLOOD. Proc Soc Exp Biol Med. 1963 Aug-Sep;113:946–949. doi: 10.3181/00379727-113-28539. [DOI] [PubMed] [Google Scholar]
  3. Bagdade J. D., Bierman E. L., Porte D., Jr The significance of basal insulin levels in the evaluation of the insulin response to glucose in diabetic and nondiabetic subjects. J Clin Invest. 1967 Oct;46(10):1549–1557. doi: 10.1172/JCI105646. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Baker N., Garfinkel A. S., Schotz M. C. Hepatic triglyceride secretion in relation to lipogenesis and free fatty acid mobilization in fasted and glucose-refed rats. J Lipid Res. 1968 Jan;9(1):1–7. [PubMed] [Google Scholar]
  5. Boden G., Soeldner J. S. A sensitive double antibody radioimmunoassay for human growth hormone (HGH): levels of serum HGH following rapid tolbutamide infusion. Diabetologia. 1967 Oct;3(5):413–421. doi: 10.1007/BF01228076. [DOI] [PubMed] [Google Scholar]
  6. Bondy P. K., James D. F., Farrar B. W. STUDIES OF THE ROLE OF THE LIVER IN HUMAN CARBOHYDRATE METABOLISM BY THE VENOUS CATHETER TECHNIC. I. NORMAL SUBJECTS UNDER FASTING CONDITIONS AND FOLLOWING THE INJECTION OF GLUCOSE. J Clin Invest. 1949 Mar;28(2):238–244. doi: 10.1172/JCI102065. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. CAESAR J., SHALDON S., CHIANDUSSI L., GUEVARA L., SHERLOCK S. The use of indocyanine green in the measurement of hepatic blood flow and as a test of hepatic function. Clin Sci. 1961 Aug;21:43–57. [PubMed] [Google Scholar]
  8. CHAPLIN H., Jr, MOLLISON P. L., VETTER H. The body/venous hematocrit ratio: its constancy over a wide hematocrit range. J Clin Invest. 1953 Dec;32(12):1309–1316. doi: 10.1172/JCI102859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cahill G. F., Jr, Herrera M. G., Morgan A. P., Soeldner J. S., Steinke J., Levy P. L., Reichard G. A., Jr, Kipnis D. M. Hormone-fuel interrelationships during fasting. J Clin Invest. 1966 Nov;45(11):1751–1769. doi: 10.1172/JCI105481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cahill G. F., Jr, Owen O. E. Starvation and survival. Trans Am Clin Climatol Assoc. 1968;79:13–20. [PMC free article] [PubMed] [Google Scholar]
  11. Cahill G. J., Jr, Owen O. E., Morgan A. P. The consumption of fuels during prolonged starvation. Adv Enzyme Regul. 1968;6:143–150. doi: 10.1016/0065-2571(68)90011-3. [DOI] [PubMed] [Google Scholar]
  12. DRENICK E. J., SWENDSEID M. E., BLAHD W. H., TUTTLE S. G. PROLONGED STARVATION AS TREATMENT FOR SEVERE OBESITY. JAMA. 1964 Jan 11;187:100–105. doi: 10.1001/jama.1964.03060150024006. [DOI] [PubMed] [Google Scholar]
  13. Felig P., Owen O. E., Wahren J., Cahill G. F., Jr Amino acid metabolism during prolonged starvation. J Clin Invest. 1969 Mar;48(3):584–594. doi: 10.1172/JCI106017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. GAMMELTOFT A. The ratio beta-hydroxybutyric acid-acetoacetic acid in the blood under various experimental conditions. Acta Physiol Scand. 1951 Oct 9;24(1):35–48. doi: 10.1111/j.1748-1716.1951.tb00825.x. [DOI] [PubMed] [Google Scholar]
  15. Goodman A. D., Fuisz R. E., Cahill G. F., Jr Renal gluconeogenesis in acidosis, alkalosis, and potassium deficiency: its possible role in regulation of renal ammonia production. J Clin Invest. 1966 Apr;45(4):612–619. doi: 10.1172/JCI105375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Goorno W. E., Rector F. C., Jr, Seldin D. W. Relation of renal gluconeogenesis to ammonia production in the dog and rat. Am J Physiol. 1967 Oct;213(4):969–974. doi: 10.1152/ajplegacy.1967.213.4.969. [DOI] [PubMed] [Google Scholar]
  17. Hagenfeldt L., Wahren J. Human forearm muscle metabolism during exercise. 3. Uptake, release and oxidation of beta-hydroxybutyrate and observations on the beta-hydroxybutyrate/acetoacetate ratio. Scand J Clin Lab Invest. 1968;21(4):314–320. doi: 10.3109/00365516809076999. [DOI] [PubMed] [Google Scholar]
  18. Hirsch J., Gallian E. Methods for the determination of adipose cell size in man and animals. J Lipid Res. 1968 Jan;9(1):110–119. [PubMed] [Google Scholar]
  19. KARAM J. H., GRODSKY G. M., FORSHAM P. H. Excessive insulin response to glucose in obese subjects as measured by immunochemical assay. Diabetes. 1963 May-Jun;12:197–204. doi: 10.2337/diab.12.3.197. [DOI] [PubMed] [Google Scholar]
  20. KIBLER R. F., TAYLOR W. J., MYERS J. D. THE EFFECT OF GLUCAGON ON NET SPANCHNIC BALANCES OF GLUCOSE, AMINO ACID NITROGEN, UREA, KETONES, ANS OXYGEN IN MAN. J Clin Invest. 1964 May;43:904–915. doi: 10.1172/JCI104976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. KREBS H. THE CROONIAN LECTURE, 1963. GLUCONEOGENESIS. Proc R Soc Lond B Biol Sci. 1964 Mar 17;159:545–564. doi: 10.1098/rspb.1964.0019. [DOI] [PubMed] [Google Scholar]
  22. LEEVY C. M., GEORGE W., LESKO W., DEYSINE M., ABBOTT C. C., HALLIGAN E. J. Observations on hepatic oxygen metabolism in man. JAMA. 1961 Nov 11;178:565–567. doi: 10.1001/jama.1961.73040450006005b. [DOI] [PubMed] [Google Scholar]
  23. Lea M. A., Weber G. Role of enzymes in homeostasis. 8. Inhibition of the activity of glycolytic enzymes by free fatty acids. J Biol Chem. 1968 Mar 25;243(6):1096–1102. [PubMed] [Google Scholar]
  24. MYERS J. D. Net splanchnic glucose production in normal man and in various disease states. J Clin Invest. 1950 Nov;29(11):1421–1429. doi: 10.1172/JCI102380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Nieth H., Schollmeyer P. Substrate-utilization of the human kidney. Nature. 1966 Mar 19;209(5029):1244–1245. doi: 10.1038/2091244a0. [DOI] [PubMed] [Google Scholar]
  26. Owen O. E., Morgan A. P., Kemp H. G., Sullivan J. M., Herrera M. G., Cahill G. F., Jr Brain metabolism during fasting. J Clin Invest. 1967 Oct;46(10):1589–1595. doi: 10.1172/JCI105650. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. RABINOWITZ D., ZIERLER K. L. Forearm metabolism in obesity and its response to intra-arterial insulin. Characterization of insulin resistance and evidence for adaptive hyperinsulinism. J Clin Invest. 1962 Dec;41:2173–2181. doi: 10.1172/JCI104676. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Salans L. B., Knittle J. L., Hirsch J. The role of adipose cell size and adipose tissue insulin sensitivity in the carbohydrate intolerance of human obesity. J Clin Invest. 1968 Jan;47(1):153–165. doi: 10.1172/JCI105705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Smith H. W., Finkelstein N., Aliminosa L., Crawford B., Graber M. THE RENAL CLEARANCES OF SUBSTITUTED HIPPURIC ACID DERIVATIVES AND OTHER AROMATIC ACIDS IN DOG AND MAN. J Clin Invest. 1945 May;24(3):388–404. doi: 10.1172/JCI101618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Solomon S. S., Ensinck J. W., Williams R. H. Effect of starvation on plasma immunoreactive insulin and non-suppressible insulin-like activity in normal and obese humans. Metabolism. 1968 Jun;17(6):528–534. doi: 10.1016/0026-0495(68)90045-0. [DOI] [PubMed] [Google Scholar]
  31. WERK E. E., Jr, McPHERSON H. T., HAMRICK L. W., Jr, MYERS J. D., ENGEL F. L. Studies on ketone metabolism in man. I. A method for the quantitative estimation of splanchnic ketone production. J Clin Invest. 1955 Aug;34(8):1256–1267. doi: 10.1172/JCI103172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Williamson J. R., Kreisberg R. A., Felts P. W. Mechanism for the stimulation of gluconeogenesis by fatty acids in perfused rat liver. Proc Natl Acad Sci U S A. 1966 Jul;56(1):247–254. doi: 10.1073/pnas.56.1.247. [DOI] [PMC free article] [PubMed] [Google Scholar]

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