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. 1986 Apr;77(4):1153–1162. doi: 10.1172/JCI112416

Enhancement of insulin action after oral glucose ingestion.

W J Kingston, J N Livingston, R T Moxley 3rd
PMCID: PMC424451  PMID: 3082935

Abstract

Previous investigations in normal humans and rats have shown an increase in insulin sensitivity and binding affinity of adipocytes isolated 1-3 h after glucose ingestion. To determine whether a rapid enhancement of the action of insulin follows glucose ingestion in vivo, the present studies have utilized 120-min 20 mU/m2 X min euglycemic insulin infusions before and after 7.5-, 15-, 25-, and 100-g oral glucose loads. Euglycemic insulin infusions after the carbohydrate challenge were begun after arterialized blood glucose and insulin values had returned to baseline. After 15- and 25-g oral glucose loads during the 20-120-min interval of insulin infusion, glucose infusion rates increased by 44 +/- 6% (P less than 0.0001) and 47 +/- 9% (P less than 0.0002), respectively. No significant differences in arterialized glucose or insulin values existed between basal and post-glucose insulin infusions. In addition, no significant differences in hepatic glucose production or counter-regulatory hormone levels were found between basal and post-glucose insulin infusions. Control infusion studies including subjects who ingested saline or mannitol failed to show an increase in insulin action. Studies were carried out to mimic the insulin curve seen after 15- and 25-g oral glucose loads. Euglycemic insulin infusions after these insulin simulation studies show a 34 +/- 7% enhancement compared to baseline euglycemic insulin infusions. These results demonstrate a rapid enhancement of insulin action after oral glucose challenge in normal humans. The insulin simulation studies suggest that insulin itself either directly or through release of another factor acts on muscle to increase insulin sensitivity. The increase in insulin action demonstrated in these investigations may represent an important regulatory mechanism to modulate tissue insulin sensitivity.

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Selected References

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

  1. ANDRES R., BALTZAN M. A., CADER G., ZIERLER K. L. Effect of insulin on carbohydrate metabolism and on potassium in the forearm of man. J Clin Invest. 1962 Jan;41:108–115. doi: 10.1172/JCI104452. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Abraira C., Lawrence A. M. The Staub-Traugott phenomenon. III. Effects of starvation. Am J Clin Nutr. 1978 Feb;31(2):213–221. doi: 10.1093/ajcn/31.2.213. [DOI] [PubMed] [Google Scholar]
  3. Arner P., Bolinder J., Ostman J. Marked increase in insulin sensitivity of human fat cells 1 hour after glucose ingestion. J Clin Invest. 1983 Mar;71(3):709–714. doi: 10.1172/JCI110817. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bar R. S., Harrison L. C., Muggeo M., Gorden P., Kahn C. R., Roth J. Regulation of insulin receptors in normal and abnormal physiology in humans. Adv Intern Med. 1979;24:23–52. [PubMed] [Google Scholar]
  5. Bergman R. N., Ader M., Finegood D. T., Pacini G. Extrapancreatic effect of somatostatin infusion to increase glucose clearance. Am J Physiol. 1984 Sep;247(3 Pt 1):E370–E379. doi: 10.1152/ajpendo.1984.247.3.E370. [DOI] [PubMed] [Google Scholar]
  6. Bratusch-Marrain P. R., Waldhäusl W. K., Gasić S., Korn A., Nowotny P. Oral glucose tolerance test: effect of different glucose loads on splanchnic carbohydrate and substrate metabolism in healthy man. Metabolism. 1980 Mar;29(3):289–295. doi: 10.1016/0026-0495(80)90071-2. [DOI] [PubMed] [Google Scholar]
  7. Cowan J. S., Hetenyi G., Jr Glucoregulatory responses in normal and diabetic dogs recorded by a new tracer method. Metabolism. 1971 Apr;20(4):360–372. doi: 10.1016/0026-0495(71)90098-9. [DOI] [PubMed] [Google Scholar]
  8. DeFronzo R. A., Jacot E., Jequier E., Maeder E., Wahren J., Felber J. P. The effect of insulin on the disposal of intravenous glucose. Results from indirect calorimetry and hepatic and femoral venous catheterization. Diabetes. 1981 Dec;30(12):1000–1007. doi: 10.2337/diab.30.12.1000. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. DeFronzo R. A., Tobin J. D., Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol. 1979 Sep;237(3):E214–E223. doi: 10.1152/ajpendo.1979.237.3.E214. [DOI] [PubMed] [Google Scholar]
  11. Dupre J., Greenidge N., McDonald T. J., Ross S. A., Rubinstein D. Inhibition of actions of glucagon in adipocytes by gastric inhibitory polypeptide. Metabolism. 1976 Nov;25(11):1197–1199. doi: 10.1016/s0026-0495(76)80002-9. [DOI] [PubMed] [Google Scholar]
  12. Ganda O. P., Soeldner J. S., Gleason R. E., Cleator I. G., Reynolds C. Metabolic effects of glucose, mannose, galactose, and fructose in man. J Clin Endocrinol Metab. 1979 Oct;49(4):616–622. doi: 10.1210/jcem-49-4-616. [DOI] [PubMed] [Google Scholar]
  13. Lahtela J. T., Särkkä P., Sotaniemi E. A. Phenobarbital treatment enhances insulin mediated glucose metabolism in man. Res Commun Chem Pathol Pharmacol. 1984 May;44(2):215–226. [PubMed] [Google Scholar]
  14. Livingston J. N., Moxley R. T., 3rd Glucose ingestion mediates a rapid increase in the insulin responsiveness of rat adipocytes. Endocrinology. 1982 Nov;111(5):1749–1751. doi: 10.1210/endo-111-5-1749. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Moxley R. T., 3rd, Griggs R. C., Goldblatt D., VanGelder V., Herr B. E., Thiel R. Decreased insulin sensitivity of forearm muscle in myotonic dystrophy. J Clin Invest. 1978 Oct;62(4):857–867. doi: 10.1172/JCI109198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Moxley R. T., 3rd, Livingston J. N., Lockwood D. H., Griggs R. C., Hill R. L. Abnormal regulation of monocyte insulin-binding affinity after glucose ingestion in patients with myotonic dystrophy. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2567–2571. doi: 10.1073/pnas.78.4.2567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Muggeo M., Bar R. S., Roth J. Change in affinity of insulin receptors following oral glucose in normal adults. J Clin Endocrinol Metab. 1977 Jun;44(6):1206–1209. doi: 10.1210/jcem-44-6-1206. [DOI] [PubMed] [Google Scholar]
  19. Pan R. M., Mauron C., Glaeser B., Wurtman R. J. Effect of various oral glucose doses on plasma neutral amino acid levels. Metabolism. 1982 Sep;31(9):937–943. doi: 10.1016/0026-0495(82)90185-8. [DOI] [PubMed] [Google Scholar]
  20. Passon P. G., Peuler J. D. A simplified radiometric assay for plasma norepinephrine and epinephrine. Anal Biochem. 1973 Feb;51(2):618–631. doi: 10.1016/0003-2697(73)90517-4. [DOI] [PubMed] [Google Scholar]
  21. Peuler J. D., Johnson G. A. Simultaneous single isotope radioenzymatic assay of plasma norepinephrine, epinephrine and dopamine. Life Sci. 1977 Sep 1;21(5):625–636. doi: 10.1016/0024-3205(77)90070-4. [DOI] [PubMed] [Google Scholar]
  22. Pozefsky T., Felig P., Tobin J. D., Soeldner J. S., Cahill G. F., Jr Amino acid balance across tissues of the forearm in postabsorptive man. Effects of insulin at two dose levels. J Clin Invest. 1969 Dec;48(12):2273–2282. doi: 10.1172/JCI106193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Radziuk J., Norwich K. H., Vranic M. Measurement and validation of nonsteady turnover rates with applications to the inulin and glucose systems. Fed Proc. 1974 Jul;33(7):1855–1864. [PubMed] [Google Scholar]
  24. 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]
  25. SCHALCH D. S., PARKER M. L. A SENSITIVE DOUBLE ANTIBODY IMMUNOASSAY FOR HUMAN GROWTH HORMONE IN PLASMA. Nature. 1964 Sep 12;203:1141–1142. doi: 10.1038/2031141a0. [DOI] [PubMed] [Google Scholar]
  26. STEELE R. Influences of glucose loading and of injected insulin on hepatic glucose output. Ann N Y Acad Sci. 1959 Sep 25;82:420–430. doi: 10.1111/j.1749-6632.1959.tb44923.x. [DOI] [PubMed] [Google Scholar]
  27. Soeldner J. S., Slone D. Critical variables in the radioimmunoassay of serum insulin using the double antibody technic. Diabetes. 1965 Dec;14(12):771–779. doi: 10.2337/diab.14.12.771. [DOI] [PubMed] [Google Scholar]
  28. UNGER R. H., EISENTRAUT A. M., McCALL M. S., MADISON L. L. Glucagon antibodies and an immunoassay for glucagon. J Clin Invest. 1961 Jul;40:1280–1289. doi: 10.1172/JCI104357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. ZIERLER K. L., RABINOWITZ D. EFFECT OF VERY SMALL CONCENTRATIONS OF INSULIN ON FOREARM METABOLISM. PERSISTENCE OF ITS ACTION ON POTASSIUM AND FREE FATTY ACIDS WITHOUT ITS EFFECT ON GLUCOSE. J Clin Invest. 1964 May;43:950–962. doi: 10.1172/JCI104981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. ZIERLER K. L., RABINOWITZ D. ROLES OF INSULIN AND GROWTH HORMONE, BASED ON STUDIES OF FOREARM METABOLISM IN MAN. Medicine (Baltimore) 1963 Nov;42:385–402. doi: 10.1097/00005792-196311000-00002. [DOI] [PubMed] [Google Scholar]

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