Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1987 Jan;79(1):207–213. doi: 10.1172/JCI112785

Lipolysis during fasting. Decreased suppression by insulin and increased stimulation by epinephrine.

M D Jensen, M W Haymond, J E Gerich, P E Cryer, J M Miles
PMCID: PMC424023  PMID: 3540009

Abstract

These studies were designed to determine whether the insulin resistance of fasting extends to its antilipolytic effects and whether fasting enhances the lipolytic effects of adrenergic stimulation independent of changes in plasma hormone and substrate concentrations. Palmitate flux was determined isotopically ([1-14C]palmitate) before and during epinephrine infusion in normal volunteers after a 14-h (day 1) and an 84-h (day 4) fast. Using a pancreatic clamp, constant plasma hormone and glucose concentrations were achieved on both study days in seven subjects. Six subjects were infused with saline and served as controls. During the pancreatic clamp, palmitate flux was greater (P less than 0.01) on day 4 than day 1, despite similar plasma insulin, glucagon, growth hormone, cortisol, epinephrine, norepinephrine, and glucose concentrations. The lipolytic response to epinephrine was greater (P less than 0.05) on day 4 than day 1 in both groups of subjects. In conclusion, lipolysis during fasting is less completely suppressed by insulin and more readily stimulated by epinephrine.

Full text

PDF
207

Selected References

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

  1. Arner P., Bolinder J., Engfeldt P., Ostman J. The antilipolytic effect of insulin in human adipose tissue in obesity, diabetes mellitus, hyperinsulinemia, and starvation. Metabolism. 1981 Aug;30(8):753–760. doi: 10.1016/0026-0495(81)90020-2. [DOI] [PubMed] [Google Scholar]
  2. Arner P., Bolinder J., Ostman J. Glucose stimulation of the antilipolytic effect of insulin in humans. Science. 1983 Jun 3;220(4601):1057–1059. doi: 10.1126/science.6342138. [DOI] [PubMed] [Google Scholar]
  3. Arner P., Engfeldt P., Nowak J. In vivo observations on the lipolytic effect of noradrenaline during therapeutic fasting. J Clin Endocrinol Metab. 1981 Dec;53(6):1207–1212. doi: 10.1210/jcem-53-6-1207. [DOI] [PubMed] [Google Scholar]
  4. Arner P., Ostman J. Changes in the adrenergic control and the rate of lipolysis of isolated human adipose tissue during fasting and after re-feeding. Acta Med Scand. 1976;200(4):273–279. [PubMed] [Google Scholar]
  5. Burns T. W., Boyer P. A., Terry B. E., Langley P. E., Robison G. A. The effect of fasting on the adrenergic receptor activity of human adipocytes. J Lab Clin Med. 1979 Sep;94(3):387–394. [PubMed] [Google Scholar]
  6. Burns T. W., Langley P. E., Terry B. E., Bylund D. B., Hoffman B. B., Tharp M. D., Lefkowitz R. J., García-Saínz J. A., Fain J. N. Pharmacological characterizations of adrenergic receptors in human adipocytes. J Clin Invest. 1981 Feb;67(2):467–475. doi: 10.1172/JCI110055. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Burns T. W., Terry B. E., Langley P. E., Robison G. A. Insulin inhibition of lipolysis of human adipocytes: the role of cyclic adenosine monophosphate. Diabetes. 1979 Nov;28(11):957–961. doi: 10.2337/diab.28.11.957. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Cahill G. F., Jr Starvation in man. N Engl J Med. 1970 Mar 19;282(12):668–675. doi: 10.1056/NEJM197003192821209. [DOI] [PubMed] [Google Scholar]
  10. DeFronzo R. A., Soman V., Sherwin R. S., Hendler R., Felig P. Insulin binding to monocytes and insulin action in human obesity, starvation, and refeeding. J Clin Invest. 1978 Jul;62(1):204–213. doi: 10.1172/JCI109108. [DOI] [PMC free article] [PubMed] [Google Scholar] [Retracted]
  11. Engfeldt P., Bolinder J., Ostman J., Arner P. Effect of fasting on insulin receptor binding and insulin action in different human subcutaneous fat depots. J Clin Endocrinol Metab. 1985 May;60(5):868–873. doi: 10.1210/jcem-60-5-868. [DOI] [PubMed] [Google Scholar]
  12. Faber O. K., Binder C., Markussen J., Heding L. G., Naithani V. K., Kuzuya H., Blix P., Horwitz D. L., Rubenstein A. H. Characterization of seven C-peptide antisera. Diabetes. 1978;27 (Suppl 1):170–177. doi: 10.2337/diab.27.1.s170. [DOI] [PubMed] [Google Scholar]
  13. Fisher M., Sherwin R. S., Hendler R., Felig P. Kinetics of glucagon in man: effects of starvation. Proc Natl Acad Sci U S A. 1976 May;73(5):1735–1739. doi: 10.1073/pnas.73.5.1735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Galster A. D., Clutter W. E., Cryer P. E., Collins J. A., Bier D. M. Epinephrine plasma thresholds for lipolytic effects in man: measurements of fatty acid transport with [l-13C]palmitic acid. J Clin Invest. 1981 Jun;67(6):1729–1738. doi: 10.1172/JCI110211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Giudicelli Y., Lacasa D., Agli B. Alterations induced by a prolonged fasting: opposite effects on the beta-adrenergic receptor-coupled adenylate-cyclase system and on lipolysis in fat cells from rat. Eur J Biochem. 1982 Jan;121(2):301–308. doi: 10.1111/j.1432-1033.1982.tb05786.x. [DOI] [PubMed] [Google Scholar]
  16. Göschke H. Mechanism of glucose intolerance during fasting: differences between lean and obese subjects. Metabolism. 1977 Oct;26(10):1147–1153. doi: 10.1016/0026-0495(77)90042-7. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Jung R. T., Shetty P. S., Barrand M., Callingham B. A., James W. P. Role of catecholamines in hypotensive response to dieting. Br Med J. 1979 Jan 6;1(6155):12–13. doi: 10.1136/bmj.1.6155.12. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kahn C. R. Insulin resistance, insulin insensitivity, and insulin unresponsiveness: a necessary distinction. Metabolism. 1978 Dec;27(12 Suppl 2):1893–1902. doi: 10.1016/s0026-0495(78)80007-9. [DOI] [PubMed] [Google Scholar]
  20. Kather H., Bieger W., Michel G., Aktories K., Jakobs K. H. Human fat cell lipolysis is primarily regulated by inhibitory modulators acting through distinct mechanisms. J Clin Invest. 1985 Oct;76(4):1559–1565. doi: 10.1172/JCI112137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kather H., Wieland E., Fischer B., Wirth A., Schlierf G. Adrenergic regulation of lipolysis in abdominal adipocytes of obese subjects during caloric restriction: reversal of catecholamine action caused by relief of endogenous inhibition. Eur J Clin Invest. 1985 Feb;15(1):30–37. doi: 10.1111/j.1365-2362.1985.tb00140.x. [DOI] [PubMed] [Google Scholar]
  22. Keller U., Schnell H., Girard J., Stauffacher W. Effect of physiological elevation of plasma growth hormone levels on ketone body kinetics and lipolysis in normal and acutely insulin-deficient man. Diabetologia. 1984 Feb;26(2):103–108. doi: 10.1007/BF00281115. [DOI] [PubMed] [Google Scholar]
  23. Kjellberg J., Ostman J. Lipolysis and glucose tolerance in obese subjects during prolonged starvation. Acta Med Scand. 1971 Sep;190(3):191–198. doi: 10.1111/j.0954-6820.1971.tb07415.x. [DOI] [PubMed] [Google Scholar]
  24. Lafontan M., Berlan M., Villeneuve A. Preponderance of alpha 2- over beta 1-adrenergic receptor sites in human fat cells is not predictive of the lipolytic effect of physiological catecholamines. J Lipid Res. 1983 Apr;24(4):429–440. [PubMed] [Google Scholar]
  25. Leiter L. A., Grose M., Yale J. F., Marliss E. B. Catecholamine responses to hypocaloric diets and fasting in obese human subjects. Am J Physiol. 1984 Aug;247(2 Pt 1):E190–E197. doi: 10.1152/ajpendo.1984.247.2.E190. [DOI] [PubMed] [Google Scholar]
  26. McGuire E. A., Helderman J. H., Tobin J. D., Andres R., Berman M. Effects of arterial versus venous sampling on analysis of glucose kinetics in man. J Appl Physiol. 1976 Oct;41(4):565–573. doi: 10.1152/jappl.1976.41.4.565. [DOI] [PubMed] [Google Scholar]
  27. Miles J., Glasscock R., Aikens J., Gerich J., Haymond M. A microfluorometric method for the determination of free fatty acids in plasma. J Lipid Res. 1983 Jan;24(1):96–99. [PubMed] [Google Scholar]
  28. Newman W. P., Brodows R. G. Insulin action during acute starvation: evidence for selective insulin resistance in normal man. Metabolism. 1983 Jun;32(6):590–596. doi: 10.1016/0026-0495(83)90029-x. [DOI] [PubMed] [Google Scholar]
  29. Ostman J., Arner P., Engfeldt P., Kager L. Regional differences in the control of lipolysis in human adipose tissue. Metabolism. 1979 Dec;28(12):1198–1205. doi: 10.1016/0026-0495(79)90131-8. [DOI] [PubMed] [Google Scholar]
  30. Ostman J., Arner P., Kimura H., Wahrenberg H., Engfeldt P. Influence of fasting on lipolytic response to adrenergic agonists and on adrenergic receptors in subcutaneous adipocytes. Eur J Clin Invest. 1984 Oct;14(5):383–391. doi: 10.1111/j.1365-2362.1984.tb01199.x. [DOI] [PubMed] [Google Scholar]
  31. Pedersen O., Hjøllund E., Sørensen N. S. Insulin receptor binding and insulin action in human fat cells: effects of obesity and fasting. Metabolism. 1982 Sep;31(9):884–895. doi: 10.1016/0026-0495(82)90177-9. [DOI] [PubMed] [Google Scholar]
  32. Pollet R. J., Levey G. S. Principles of membrane receptor physiology and their application to clinical medicine. Ann Intern Med. 1980 May;92(5):663–680. doi: 10.7326/0003-4819-92-5-663. [DOI] [PubMed] [Google Scholar]
  33. RANDLE P. J., GARLAND P. B., HALES C. N., NEWSHOLME E. A. The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet. 1963 Apr 13;1(7285):785–789. doi: 10.1016/s0140-6736(63)91500-9. [DOI] [PubMed] [Google Scholar]
  34. Rizza R. A., Mandarino L. J., Gerich J. E. Dose-response characteristics for effects of insulin on production and utilization of glucose in man. Am J Physiol. 1981 Jun;240(6):E630–E639. doi: 10.1152/ajpendo.1981.240.6.E630. [DOI] [PubMed] [Google Scholar]
  35. Scheen A., Cession-Fossion A., Scheen-Lavigne M., Luyckx A. Effect of protein-supplemented fasting on metabolic and hormonal responses to epinephrine infusion in obese subjects. Horm Metab Res. 1982 May;14(5):240–245. doi: 10.1055/s-2007-1018982. [DOI] [PubMed] [Google Scholar]
  36. Shah S. D., Clutter W. E., Cryer P. E. External and internal standards in the single-isotope derivative (radioenzymatic) measurement of plasma norepinephrine and epinephrine. J Lab Clin Med. 1985 Dec;106(6):624–629. [PubMed] [Google Scholar]
  37. Villeneuve A., Carpene C., Berlan M., Lafontan M. Lack of desensitization of alpha-2-mediated inhibition of lipolysis in fat cells after acute and chronic treatment with clonidine. J Pharmacol Exp Ther. 1985 May;233(2):433–440. [PubMed] [Google Scholar]
  38. Young J. B., Rosa R. M., Landsberg L. Dissociation of sympathetic nervous system and adrenal medullary responses. Am J Physiol. 1984 Jul;247(1 Pt 1):E35–E40. doi: 10.1152/ajpendo.1984.247.1.E35. [DOI] [PubMed] [Google Scholar]
  39. Zapf J., Waldvogel M., Froesch E. R. Increased sensitivity of rat adipose tissue to the lipolytic action of epinephrine during fasting and its reversal during re-feeding. FEBS Lett. 1977 Apr 1;76(1):135–138. doi: 10.1016/0014-5793(77)80137-3. [DOI] [PubMed] [Google Scholar]

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

RESOURCES