Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1996 Aug 1;98(3):692–697. doi: 10.1172/JCI118840

Phenylalanine kinetics in human adipose tissue.

S W Coppack 1, M Persson 1, J M Miles 1
PMCID: PMC507478  PMID: 8698860

Abstract

Very little is known about the regulation of protein metabolism in adipose tissue. In this study systemic, adipose tissue, and forearm phenylalanine kinetics were determined in healthy postabsorptive volunteers before and during a 2-h glucose infusion (7 mg.kg-1.min-1). [3H]Phenylalanine was infused and blood was sampled from a radial artery, a subcutaneous abdominal vein, and a deep forearm vein. Adipose tissue and forearm blood flow were measured with 133Xe and plethysmography, respectively, and body fat mass was determined by dual energy x-ray absorptiometry. During glucose infusion, glucose concentration increased from 86 +/- 2 to 228 +/- 13 mg/dl and insulin concentration increased from 6.6 +/- 0.6 to 35.0 +/- 3.9 mU/liter, both P < 0.001. Systemic phenylalanine appearance decreased from 40.3 +/- 1.9 to 37.0 +/- 1.6 mumol/min during glucose infusion (P < 0.05). Baseline whole body adipose tissue phenylalanine release (5.2 +/- 1.4 mumol/min) was approximately 12% of systemic phenylalanine appearance and decreased (P < 0.05) to 2.3 +/- 0.9 mumol/min during glucose infusion. In contrast, phenylalanine release from the forearm did not change during glucose infusion. These results indicate that adipose tissue is a small but significant contributor to systemic phenylalanine appearance. Phenylalanine release from adipose tissue like lipolysis, is relatively sensitive to hyperinsulinemia.

Full Text

The Full Text of this article is available as a PDF (157.9 KB).

Selected References

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

  1. ANDRES R., CADER G., ZIERLER K. L. The quantitatively minor role of carbohydrate in oxidative metabolism by skeletal muscle in intact man in the basal state; measurements of oxygen and glucose uptake and carbon dioxide and lactate production in the forearm. J Clin Invest. 1956 Jun;35(6):671–682. doi: 10.1172/JCI103324. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Arner P., Bülow J. Assessment of adipose tissue metabolism in man: comparison of Fick and microdialysis techniques. Clin Sci (Lond) 1993 Sep;85(3):247–256. doi: 10.1042/cs0850247. [DOI] [PubMed] [Google Scholar]
  3. Barrett E. J., Revkin J. H., Young L. H., Zaret B. L., Jacob R., Gelfand R. A. An isotopic method for measurement of muscle protein synthesis and degradation in vivo. Biochem J. 1987 Jul 1;245(1):223–228. doi: 10.1042/bj2450223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Binder C., Lauritzen T., Faber O., Pramming S. Insulin pharmacokinetics. Diabetes Care. 1984 Mar-Apr;7(2):188–199. doi: 10.2337/diacare.7.2.188. [DOI] [PubMed] [Google Scholar]
  5. Bleiberg B., Beers T. R., Persson M., Miles J. M. Systemic and regional acetate kinetics in dogs. Am J Physiol. 1992 Feb;262(2 Pt 1):E197–E202. doi: 10.1152/ajpendo.1992.262.2.E197. [DOI] [PubMed] [Google Scholar]
  6. Bülow J., Jelnes R., Astrup A., Madsen J., Vilmann P. Tissue/blood partition coefficients for xenon in various adipose tissue depots in man. Scand J Clin Lab Invest. 1987 Feb;47(1):1–3. doi: 10.1080/00365518709168861. [DOI] [PubMed] [Google Scholar]
  7. COLES D. R., COOPER K. E., MOTTRAM R. F., OCCLESHAW J. V. The source of blood samples withdrawn from deep forearm veins via catheters passed upstream from the median cubital vein. J Physiol. 1958 Jul 14;142(2):323–328. doi: 10.1113/jphysiol.1958.sp006019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. COOPER K. E., EDHOLM O. G., MOTTRAM R. F. The blood flow in skin and muscle of the human forearm. J Physiol. 1955 May 27;128(2):258–267. doi: 10.1113/jphysiol.1955.sp005304. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Castellino P., Luzi L., Simonson D. C., Haymond M., DeFronzo R. A. Effect of insulin and plasma amino acid concentrations on leucine metabolism in man. Role of substrate availability on estimates of whole body protein synthesis. J Clin Invest. 1987 Dec;80(6):1784–1793. doi: 10.1172/JCI113272. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Clarke J. T., Bier D. M. The conversion of phenylalanine to tyrosine in man. Direct measurement by continuous intravenous tracer infusions of L-[ring-2H5]phenylalanine and L-[1-13C] tyrosine in the postabsorptive state. Metabolism. 1982 Oct;31(10):999–1005. doi: 10.1016/0026-0495(82)90142-1. [DOI] [PubMed] [Google Scholar]
  11. Coppack S. W., Evans R. D., Fisher R. M., Frayn K. N., Gibbons G. F., Humphreys S. M., Kirk M. L., Potts J. L., Hockaday T. D. Adipose tissue metabolism in obesity: lipase action in vivo before and after a mixed meal. Metabolism. 1992 Mar;41(3):264–272. doi: 10.1016/0026-0495(92)90269-g. [DOI] [PubMed] [Google Scholar]
  12. Coppack S. W., Fisher R. M., Gibbons G. F., Humphreys S. M., McDonough M. J., Potts J. L., Frayn K. N. Postprandial substrate deposition in human forearm and adipose tissues in vivo. Clin Sci (Lond) 1990 Oct;79(4):339–348. doi: 10.1042/cs0790339. [DOI] [PubMed] [Google Scholar]
  13. Coppack S. W., Jensen M. D., Miles J. M. In vivo regulation of lipolysis in humans. J Lipid Res. 1994 Feb;35(2):177–193. [PubMed] [Google Scholar]
  14. Dagenais G. R., Tancredi R. G., Zierler K. L. Free fatty acid oxidation by forearm muscle at rest, and evidence for an intramuscular lipid pool in the human forearm. J Clin Invest. 1976 Aug;58(2):421–431. doi: 10.1172/JCI108486. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. De Feo P., Horber F. F., Haymond M. W. Meal stimulation of albumin synthesis: a significant contributor to whole body protein synthesis in humans. Am J Physiol. 1992 Oct;263(4 Pt 1):E794–E799. doi: 10.1152/ajpendo.1992.263.4.E794. [DOI] [PubMed] [Google Scholar]
  16. Flakoll P. J., Hill J. O., Abumrad N. N. Acute hyperglycemia enhances proteolysis in normal man. Am J Physiol. 1993 Nov;265(5 Pt 1):E715–E721. doi: 10.1152/ajpendo.1993.265.5.E715. [DOI] [PubMed] [Google Scholar]
  17. Frayn K. N., Coppack S. W., Humphreys S. M., Whyte P. L. Metabolic characteristics of human adipose tissue in vivo. Clin Sci (Lond) 1989 May;76(5):509–516. doi: 10.1042/cs0760509. [DOI] [PubMed] [Google Scholar]
  18. Gelfand R. A., Barrett E. J. Effect of physiologic hyperinsulinemia on skeletal muscle protein synthesis and breakdown in man. J Clin Invest. 1987 Jul;80(1):1–6. doi: 10.1172/JCI113033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Herbert V., Lau K. S., Gottlieb C. W., Bleicher S. J. Coated charcoal immunoassay of insulin. J Clin Endocrinol Metab. 1965 Oct;25(10):1375–1384. doi: 10.1210/jcem-25-10-1375. [DOI] [PubMed] [Google Scholar]
  20. Horber F. F., Haymond M. W. Human growth hormone prevents the protein catabolic side effects of prednisone in humans. J Clin Invest. 1990 Jul;86(1):265–272. doi: 10.1172/JCI114694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Horber F. F., Horber-Feyder C. M., Krayer S., Schwenk W. F., Haymond M. W. Plasma reciprocal pool specific activity predicts that of intracellular free leucine for protein synthesis. Am J Physiol. 1989 Sep;257(3 Pt 1):E385–E399. doi: 10.1152/ajpendo.1989.257.3.E385. [DOI] [PubMed] [Google Scholar]
  22. Irving C. S., Thomas M. R., Malphus E. W., Marks L., Wong W. W., Boutton T. W., Klein P. D. Lysine and protein metabolism in young women. Subdivision based on the novel use of multiple stable isotopic labels. J Clin Invest. 1986 Apr;77(4):1321–1331. doi: 10.1172/JCI112437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Jackson R. A., Roshania R. D., Hawa M. I., Sim B. M., DiSilvio L. Impact of glucose ingestion on hepatic and peripheral glucose metabolism in man: an analysis based on simultaneous use of the forearm and double isotope techniques. J Clin Endocrinol Metab. 1986 Sep;63(3):541–549. doi: 10.1210/jcem-63-3-541. [DOI] [PubMed] [Google Scholar]
  24. Jensen M. D., Caruso M., Heiling V., Miles J. M. Insulin regulation of lipolysis in nondiabetic and IDDM subjects. Diabetes. 1989 Dec;38(12):1595–1601. doi: 10.2337/diab.38.12.1595. [DOI] [PubMed] [Google Scholar]
  25. Jensen M. D., Haymond M. W. Protein metabolism in obesity: effects of body fat distribution and hyperinsulinemia on leucine turnover. Am J Clin Nutr. 1991 Jan;53(1):172–176. doi: 10.1093/ajcn/53.1.172. [DOI] [PubMed] [Google Scholar]
  26. Jensen M. D., Kanaley J. A., Roust L. R., O'Brien P. C., Braun J. S., Dunn W. L., Wahner H. W. Assessment of body composition with use of dual-energy x-ray absorptiometry: evaluation and comparison with other methods. Mayo Clin Proc. 1993 Sep;68(9):867–873. doi: 10.1016/s0025-6196(12)60695-8. [DOI] [PubMed] [Google Scholar]
  27. Kaijser L., Rössner S. Removal of exogenous triglycerides in human forearm muscle and subcutaneous tissue. Acta Med Scand. 1975 Apr;197(4):289–294. doi: 10.1111/j.0954-6820.1975.tb04919.x. [DOI] [PubMed] [Google Scholar]
  28. Lecavalier L., Horber F. F., Haymond M. W. Determination of plasma concentrations and 3H-specific activity of phenylalanine in plasma using high-performance liquid chromatography. J Chromatogr. 1989 Jul 21;491(2):410–417. doi: 10.1016/s0378-4347(00)82859-5. [DOI] [PubMed] [Google Scholar]
  29. Louard R. J., Fryburg D. A., Gelfand R. A., Barrett E. J. Insulin sensitivity of protein and glucose metabolism in human forearm skeletal muscle. J Clin Invest. 1992 Dec;90(6):2348–2354. doi: 10.1172/JCI116124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Matthews D. E., Motil K. J., Rohrbaugh D. K., Burke J. F., Young V. R., Bier D. M. Measurement of leucine metabolism in man from a primed, continuous infusion of L-[1-3C]leucine. Am J Physiol. 1980 May;238(5):E473–E479. doi: 10.1152/ajpendo.1980.238.5.E473. [DOI] [PubMed] [Google Scholar]
  31. Miles J. M., Nissen S. L., Gerich J. E., Haymond M. W. Effects of epinephrine infusion on leucine and alanine kinetics in humans. Am J Physiol. 1984 Aug;247(2 Pt 1):E166–E172. doi: 10.1152/ajpendo.1984.247.2.E166. [DOI] [PubMed] [Google Scholar]
  32. Møller N., Butler P. C., Antsiferov M. A., Alberti K. G. Effects of growth hormone on insulin sensitivity and forearm metabolism in normal man. Diabetologia. 1989 Feb;32(2):105–110. doi: 10.1007/BF00505182. [DOI] [PubMed] [Google Scholar]
  33. Nielsen S. L. Adipose tissue blood flow determined by the washout of locally injected 133 Xenon. Scand J Clin Lab Invest. 1972 Feb;29(1):31–36. doi: 10.3109/00365517209081052. [DOI] [PubMed] [Google Scholar]
  34. Nurjhan N., Campbell P. J., Kennedy F. P., Miles J. M., Gerich J. E. Insulin dose-response characteristics for suppression of glycerol release and conversion to glucose in humans. Diabetes. 1986 Dec;35(12):1326–1331. doi: 10.2337/diab.35.12.1326. [DOI] [PubMed] [Google Scholar]
  35. O'Keefe S. J., Sender P. M., James W. P. "Catabolic" loss of body nitrogen in response to surgery. Lancet. 1974 Nov 2;2(7888):1035–1038. doi: 10.1016/s0140-6736(74)92149-7. [DOI] [PubMed] [Google Scholar]
  36. Peiris A. N., Mueller R. A., Smith G. A., Struve M. F., Kissebah A. H. Splanchnic insulin metabolism in obesity. Influence of body fat distribution. J Clin Invest. 1986 Dec;78(6):1648–1657. doi: 10.1172/JCI112758. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Quaade F., Larsen O. A., Lassen N. A., Nielsen S. L. Observations on the influence of glucose upon subcutaneous adipose tissue blood flow. Acta Med Scand Suppl. 1967;476:85–90. doi: 10.1111/j.0954-6820.1967.tb12687.x. [DOI] [PubMed] [Google Scholar]
  38. Robertson D. A., Singh B. M., Baddeley R. M., Nattrass M. Metabolic abnormalities in obese patients with impaired glucose tolerance. Diabet Med. 1990 Jan;7(1):45–49. doi: 10.1111/j.1464-5491.1990.tb01306.x. [DOI] [PubMed] [Google Scholar]
  39. Rodriguez N., Schwenk W. F., Beaufrere B., Miles J. M., Haymond M. W. Trioctanoin infusion increases in vivo leucine oxidation: a lesson in isotope modeling. Am J Physiol. 1986 Sep;251(3 Pt 1):E343–E348. doi: 10.1152/ajpendo.1986.251.3.E343. [DOI] [PubMed] [Google Scholar]
  40. Rössner S., Eklund B., Kaijser L., Olsson A. G., Walldius G. Removal of exogenous plasma triglycerides in forearm muscle and subcutaneous tissue of hyper-and normotriglyceridaemic men. Eur J Clin Invest. 1976 Jul 30;6(4):299–305. doi: 10.1111/j.1365-2362.1976.tb00524.x. [DOI] [PubMed] [Google Scholar]
  41. Simmons P. S., Miles J. M., Gerich J. E., Haymond M. W. Increased proteolysis. An effect of increases in plasma cortisol within the physiologic range. J Clin Invest. 1984 Feb;73(2):412–420. doi: 10.1172/JCI111227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Tessari P., Inchiostro S., Biolo G., Vincenti E., Sabadin L. Effects of acute systemic hyperinsulinemia on forearm muscle proteolysis in healthy man. J Clin Invest. 1991 Jul;88(1):27–33. doi: 10.1172/JCI115287. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Tessari P., Pehling G., Nissen S. L., Gerich J. E., Service F. J., Rizza R. A., Haymond M. W. Regulation of whole-body leucine metabolism with insulin during mixed-meal absorption in normal and diabetic humans. Diabetes. 1988 May;37(5):512–519. doi: 10.2337/diab.37.5.512. [DOI] [PubMed] [Google Scholar]
  44. Tessari P., Trevisan R., Inchiostro S., Biolo G., Nosadini R., De Kreutzenberg S. V., Duner E., Tiengo A., Crepaldi G. Dose-response curves of effects of insulin on leucine kinetics in humans. Am J Physiol. 1986 Sep;251(3 Pt 1):E334–E342. doi: 10.1152/ajpendo.1986.251.3.E334. [DOI] [PubMed] [Google Scholar]
  45. Wahren J. Quantitative aspects of blood flow and oxygen uptake in the human forearm during rhythmic exercise. Acta Physiol Scand Suppl. 1966;269:1–93. [PubMed] [Google Scholar]
  46. Wahrenberg H., Lönnqvist F., Arner P. Mechanisms underlying regional differences in lipolysis in human adipose tissue. J Clin Invest. 1989 Aug;84(2):458–467. doi: 10.1172/JCI114187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Wolfe R. R., Goodenough R. D., Burke J. F., Wolfe M. H. Response of protein and urea kinetics in burn patients to different levels of protein intake. Ann Surg. 1983 Feb;197(2):163–171. doi: 10.1097/00000658-198302000-00007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Young L. H., McNulty P. H., Morgan C., Deckelbaum L. I., Zaret B. L., Barrett E. J. Myocardial protein turnover in patients with coronary artery disease. Effect of branched chain amino acid infusion. J Clin Invest. 1991 Feb;87(2):554–560. doi: 10.1172/JCI115030. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES