Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1988 Aug 1;253(3):625–629. doi: 10.1042/bj2530625

Insulin-stimulated alpha-(methyl)aminoisobutyric acid uptake in skeletal muscle. Evidence for a short-term activation of uptake independent of Na+ electrochemical gradient and protein synthesis.

A Gumà 1, X Testar 1, M Palacín 1, A Zorzano 1
PMCID: PMC1149352  PMID: 2460082

Abstract

1. The present study was designed to explore the mechanisms by which insulin stimulates system A of amino acid transport in extensor digitorum longus (EDL) muscles, by using a system A analogue, alpha-(methyl)aminoisobutyric acid (MeAIB). 2. Insulin stimulation of MeAIB uptake was noted after only 30 min of incubation and was maximal at 60 min. Kinetics of the insulin effect on MeAIB uptake were characterized by an increased Vmax. without modification of Km for MeAIB. 3. Incubation of EDL muscles with cycloheximide for 90 min did not modify MeAIB uptake in either the presence or the absence of insulin, indicating the independence of insulin action from protein synthesis de novo. Incubations for 180 min with cycloheximide caused a decrease in basal MeAIB uptake; however, the percentage stimulation of amino acid transport by insulin was unaltered. Basal MeAIB uptake was increased by incubation for 180 min, but under these conditions no change in the percentage effect of insulin was found. 4. Ouabain, gramicidin D, or both, markedly decreased basal MeAIB uptake by EDL muscle, but the percentage effect of insulin was unaltered. 5. We conclude that insulin action on amino acid transport through system A in muscle is rapid, is characterized by an increased Vmax., and is independent of protein synthesis de novo and the Na+ electrochemical gradient. Our data are compatible with insulin acting directly on the system A transporter.

Full text

PDF
625

Selected References

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

  1. AKEDO H., CHRISTENSEN H. N. Nature of insulin action on amino acid uptake by the isolated diaphragm. J Biol Chem. 1962 Jan;237:118–122. [PubMed] [Google Scholar]
  2. Arvill A., Ahrén K. Effects of insulin on the intact levator ani muscle of the rat. I. Effects on the accumulation of alpha-aminoisobutyric acid and D-xylose. Acta Endocrinol (Copenh) 1967 Oct;56(2):279–294. doi: 10.1530/acta.0.0560279. [DOI] [PubMed] [Google Scholar]
  3. Clausen T., Flatman J. A. Effects of insulin and epinephrine on Na+-K+ and glucose transport in soleus muscle. Am J Physiol. 1987 Apr;252(4 Pt 1):E492–E499. doi: 10.1152/ajpendo.1987.252.4.E492. [DOI] [PubMed] [Google Scholar]
  4. Clausen T., Kohn P. G. The effect of insulin on the transport of sodium and potassium in rat soleus muscle. J Physiol. 1977 Feb;265(1):19–42. doi: 10.1113/jphysiol.1977.sp011703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cushman S. W., Wardzala L. J. Potential mechanism of insulin action on glucose transport in the isolated rat adipose cell. Apparent translocation of intracellular transport systems to the plasma membrane. J Biol Chem. 1980 May 25;255(10):4758–4762. [PubMed] [Google Scholar]
  6. Davis R. J., Corvera S., Czech M. P. Insulin stimulates cellular iron uptake and causes the redistribution of intracellular transferrin receptors to the plasma membrane. J Biol Chem. 1986 Jul 5;261(19):8708–8711. [PubMed] [Google Scholar]
  7. Elsas L. J., 2nd, MacDonell R. C., Jr, Rosenberg L. E. Influence of age on insulin stimulation of amino acid uptake in rat diaphragm. J Biol Chem. 1971 Nov;246(21):6452–6459. [PubMed] [Google Scholar]
  8. Elsas L. J., Albrecht I., Rosenberg L. E. Insulin stimulation of amino acid uptake in rat diaphragm. Relationship to protein sythesis. J Biol Chem. 1968 Apr 25;243(8):1846–1853. [PubMed] [Google Scholar]
  9. Elsas L. J., Wheeler F. B., Danner D. J., DeHaan R. L. Amino acid transport by aggregates of cultured chicken heart cells. Effect of insulin. J Biol Chem. 1975 Dec 25;250(24):9381–9390. [PubMed] [Google Scholar]
  10. Fehlmann M., Le Cam A., Freychet P. Insulin and glucagon stimulation of amino acid transport in isolated rat hepatocytes. Synthesis of a high affinity component of transport. J Biol Chem. 1979 Oct 25;254(20):10431–10437. [PubMed] [Google Scholar]
  11. Fehlmann M., Samson M., Koch K. S., Leffert H. L., Freychet P. The effect of amiloride on hormonal regulation of amino acid transport in isolated and cultured adult rat hepatocytes. Biochim Biophys Acta. 1981 Mar 20;642(1):88–95. doi: 10.1016/0005-2736(81)90140-1. [DOI] [PubMed] [Google Scholar]
  12. Flatman J. A., Clausen T. Combined effects of adrenaline and insulin on active electrogenic Na+-K+ transport in rat soleus muscle. Nature. 1979 Oct 18;281(5732):580–581. doi: 10.1038/281580a0. [DOI] [PubMed] [Google Scholar]
  13. Forsayeth J. R., Gould M. K. Inhibition of insulin-stimulated xylose uptake in rat soleus muscle by cycloheximide. Diabetologia. 1983 Nov;25(5):429–432. doi: 10.1007/BF00282523. [DOI] [PubMed] [Google Scholar]
  14. Goldberg A. L., Jablecki C., Li J. B. Trophic functions of the neuron. 3. Mechanisms of neurotrophic interactions. Effects of use and disuse on amino acid transport and protein turnover in muscle. Ann N Y Acad Sci. 1974 Mar 22;228(0):190–201. doi: 10.1111/j.1749-6632.1974.tb20510.x. [DOI] [PubMed] [Google Scholar]
  15. Guidotti G. G., Borghetti A. F., Gazzola G. C. The regulation of amino acid transport in animal cells. Biochim Biophys Acta. 1978 Dec 15;515(4):329–366. doi: 10.1016/0304-4157(78)90009-6. [DOI] [PubMed] [Google Scholar]
  16. Guidotti G. G., Gazzola G. C., Borghetti A. F., Franchi-Gazzola R. Adaptive regulation of amino acid transport across the cell membrane in avian and mammalian tissues. Biochim Biophys Acta. 1975 Oct 6;406(2):264–279. doi: 10.1016/0005-2736(75)90009-7. [DOI] [PubMed] [Google Scholar]
  17. James D. E., Lederman L., Pilch P. F. Purification of insulin-dependent exocytic vesicles containing the glucose transporter. J Biol Chem. 1987 Aug 25;262(24):11817–11824. [PubMed] [Google Scholar]
  18. KIPNIS D. M., NOALL M. W. Stimulation of amino acid transport by insulin in the isolated rat diaphragm. Biochim Biophys Acta. 1958 Apr;28(1):226–227. doi: 10.1016/0006-3002(58)90466-9. [DOI] [PubMed] [Google Scholar]
  19. Karnieli E., Zarnowski M. J., Hissin P. J., Simpson I. A., Salans L. B., Cushman S. W. Insulin-stimulated translocation of glucose transport systems in the isolated rat adipose cell. Time course, reversal, insulin concentration dependency, and relationship to glucose transport activity. J Biol Chem. 1981 May 25;256(10):4772–4777. [PubMed] [Google Scholar]
  20. Kletzien R. F., Pariza M. W., Becker J. E., Potter V. R., Butcher F. R. Induction of amino acid transport in primary cultures of adult rat liver parenchymal cells by insulin. J Biol Chem. 1976 May 25;251(10):3014–3020. [PubMed] [Google Scholar]
  21. Kono T., Robinson F. W., Sarver J. A. Insulin-sensitive phosphodiesterase. Its localization, hormonal stimulation, and oxidative stabilization. J Biol Chem. 1975 Oct 10;250(19):7826–7835. [PubMed] [Google Scholar]
  22. Kono T., Suzuki K., Dansey L. E., Robinson F. W., Blevins T. L. Energy-dependent and protein synthesis-independent recycling of the insulin-sensitive glucose transport mechanism in fat cells. J Biol Chem. 1981 Jun 25;256(12):6400–6407. [PubMed] [Google Scholar]
  23. Kristensen L. O., Folke M. Effects of perturbation of the Na+ electrochemical gradient on influx and efflux of alanine in isolated rat hepatocytes. Biochim Biophys Acta. 1986 Feb 13;855(1):49–57. doi: 10.1016/0005-2736(86)90187-2. [DOI] [PubMed] [Google Scholar]
  24. Le Marchand-Brustel Y., Moutard N., Freychet P. Aminoisobutyric acid transport in soleus muscles of lean and gold thioglucose-obese mice. Am J Physiol. 1982 Jul;243(1):E74–E79. doi: 10.1152/ajpendo.1982.243.1.E74. [DOI] [PubMed] [Google Scholar]
  25. Logan W. J., Klip A., Gagalang E. Regulation of amino acid transport in L6 muscle cells: I. Stimulation of transport system A by amino acid deprivation. J Cell Physiol. 1982 Aug;112(2):229–236. doi: 10.1002/jcp.1041120211. [DOI] [PubMed] [Google Scholar]
  26. Loten E. G., Sneyd J. G. An effect of insulin on adipose-tissue adenosine 3':5'-cyclic monophosphate phosphodiesterase. Biochem J. 1970 Nov;120(1):187–193. doi: 10.1042/bj1200187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Maizels E. Z., Ruderman N. B., Goodman M. N., Lau D. Effect of acetoacetate on glucose metabolism in the soleus and extensor digitorum longus muscles of the rat. Biochem J. 1977 Mar 15;162(3):557–568. doi: 10.1042/bj1620557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Manchester K. L., Guidotti G. G., Borghetti A. F., Lüneburg B. Evaluation of kinetic parameters for uptake of amino acids by cells: effect of insulin on the accumulation of aminoisobutyrate and cycloleucine by isolated rat diaphragm muscle and chick embryo hearts. Biochim Biophys Acta. 1971 Jul 6;241(1):226–241. doi: 10.1016/0005-2736(71)90319-1. [DOI] [PubMed] [Google Scholar]
  29. Maroni B. J., Karapanos G., Mitch W. E. System A amino acid transport in incubated muscle: effects of insulin and acute uremia. Am J Physiol. 1986 Jul;251(1 Pt 2):F74–F80. doi: 10.1152/ajprenal.1986.251.1.F74. [DOI] [PubMed] [Google Scholar]
  30. Moore R. D. Effect of insulin upon the sodium pump in frog skeletal muscle. J Physiol. 1973 Jul;232(1):23–45. doi: 10.1113/jphysiol.1973.sp010255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Oka Y., Mottola C., Oppenheimer C. L., Czech M. P. Insulin activates the appearance of insulin-like growth factor II receptors on the adipocyte cell surface. Proc Natl Acad Sci U S A. 1984 Jul;81(13):4028–4032. doi: 10.1073/pnas.81.13.4028. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Prentki M., Crettaz M., Jeanrenaud B. Role of microtubules in insulin and glucagon stimulation of amino acid transport in isolated rat hepatocytes. J Biol Chem. 1981 May 10;256(9):4336–4340. [PubMed] [Google Scholar]
  33. Rosić N. K., Standaert M. L., Pollet R. J. The mechanism of insulin stimulation of (Na+,K+)-ATPase transport activity in muscle. J Biol Chem. 1985 May 25;260(10):6206–6212. [PubMed] [Google Scholar]
  34. Suzuki K., Kono T. Evidence that insulin causes translocation of glucose transport activity to the plasma membrane from an intracellular storage site. Proc Natl Acad Sci U S A. 1980 May;77(5):2542–2545. doi: 10.1073/pnas.77.5.2542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Wardzala L. J., Simpson I. A., Rechler M. M., Cushman S. W. Potential mechanism of the stimulatory action of insulin on insulin-like growth factor II binding to the isolated rat adipose cell. Apparent redistribution of receptors cycling between a large intracellular pool and the plasma membrane. J Biol Chem. 1984 Jul 10;259(13):8378–8383. [PubMed] [Google Scholar]
  36. ZIERLER K. L. Effect of insulin on membrane potential and potassium content of rat muscle. Am J Physiol. 1959 Sep;197:515–523. doi: 10.1152/ajplegacy.1959.197.3.515. [DOI] [PubMed] [Google Scholar]
  37. Zierler K., Rogus E. Insulin does not hyperpolarize rat muscle by means of a ouabain-inhibitable process. Am J Physiol. 1981 Sep;241(3):C145–C149. doi: 10.1152/ajpcell.1981.241.3.C145. [DOI] [PubMed] [Google Scholar]
  38. Zorzano A., Balon T. W., Garetto L. P., Goodman M. N., Ruderman N. B. Muscle alpha-aminoisobutyric acid transport after exercise: enhanced stimulation by insulin. Am J Physiol. 1985 May;248(5 Pt 1):E546–E552. doi: 10.1152/ajpendo.1985.248.5.E546. [DOI] [PubMed] [Google Scholar]
  39. Zorzano A., Balon T. W., Goodman M. N., Ruderman N. B. Additive effects of prior exercise and insulin on glucose and AIB uptake by rat muscle. Am J Physiol. 1986 Jul;251(1 Pt 1):E21–E26. doi: 10.1152/ajpendo.1986.251.1.E21. [DOI] [PubMed] [Google Scholar]
  40. Zorzano A., Balon T. W., Goodman M. N., Ruderman N. B. Insulin and exercise stimulate muscle alpha-aminoisobutyric acid transport by a Na+-K+-ATPase independent pathway. Biochem Biophys Res Commun. 1986 Feb 13;134(3):1342–1349. doi: 10.1016/0006-291x(86)90397-9. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES