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. 1995 May;95(5):2232–2238. doi: 10.1172/JCI117913

A noninvasive method to measure splanchnic glucose uptake after oral glucose administration.

B Ludvik 1, J J Nolan 1, A Roberts 1, J Baloga 1, M Joyce 1, J M Bell 1, J M Olefsky 1
PMCID: PMC295835  PMID: 7738188

Abstract

We have developed a noninvasive method to estimate splanchnic glucose uptake (SGU) in humans (oral glucose clamp technique [OG-CLAMP]), which combines a hyperinsulinemic clamp with an oral glucose load (oral glucose tolerance test). We validated this method in 12 nondiabetic subjects using hepatic vein catheterization (HVC) during an oral glucose tolerance test. During HVC, splanchnic blood flow increased from 1,395 +/- 64 to 1,935 +/- 109 ml/min, returning to basal after 180 min and accounted for 45 +/- 7% of SGU in lean and 19 +/- 5% in obese subjects (P < 0.05). SGU estimated during the OG-CLAMP was 22 +/- 2% of the glucose load, and this was significantly correlated (r = 0.90, P < 0.0001) with SGU (35 +/- 4%) and with first pass SGU (24 +/- 3%; r = 0.83, P < 0.001) measured during HVC. SGU was higher in obese than in lean subjects during OG-CLAMP (27 +/- 1% vs 18 +/- 3%, P < 0.01) and HVC (44 +/- 4% vs 26 +/- 5%, P < 0.05). In conclusion, SGU during the OG-CLAMP is well correlated to SGU measured during HVC. An increase in splanchnic blood flow is a major contributor to SGU in lean subjects. SGU is increased in obese subjects as measured by both methods.

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Selected References

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  1. Adkins-Marshall B. A., Myers S. R., Hendrick G. K., Williams P. E., Triebwasser K., Floyd B., Cherrington A. D. Interaction between insulin and glucose-delivery route in regulation of net hepatic glucose uptake in conscious dogs. Diabetes. 1990 Jan;39(1):87–95. doi: 10.2337/diacare.39.1.87. [DOI] [PubMed] [Google Scholar]
  2. Adkins B. A., Myers S. R., Hendrick G. K., Stevenson R. W., Williams P. E., Cherrington A. D. Importance of the route of intravenous glucose delivery to hepatic glucose balance in the conscious dog. J Clin Invest. 1987 Feb;79(2):557–565. doi: 10.1172/JCI112847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bhathena S. J., Timmers K. I., Oie H. K., Voyles N. R., Recant L. Cytosolic insulin-degrading activity in islet-derived tumor cell lines and in normal rat islets. Diabetes. 1985 Feb;34(2):121–128. doi: 10.2337/diab.34.2.121. [DOI] [PubMed] [Google Scholar]
  4. Butler P. C., Rizza R. A. Contribution to postprandial hyperglycemia and effect on initial splanchnic glucose clearance of hepatic glucose cycling in glucose-intolerant or NIDDM patients. Diabetes. 1991 Jan;40(1):73–81. [PubMed] [Google Scholar]
  5. CUMMINS A. J. Absorption of glucose and methionine from the human intestine; the influence of the glucose concentration in the blood and in the intestinal lumen. J Clin Invest. 1952 Oct;31(10):928–937. doi: 10.1172/JCI102681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cherrington A. D., Pagliassotti M. J., Myers S. R., Adkins-Marshall B., McGuinness O. P. Factors which regulate net hepatic glucose uptake in vivo. JPEN J Parenter Enteral Nutr. 1991 May-Jun;15(3):71S–73S. doi: 10.1177/014860719101500371S. [DOI] [PubMed] [Google Scholar]
  7. Consoli A. Role of liver in pathophysiology of NIDDM. Diabetes Care. 1992 Mar;15(3):430–441. doi: 10.2337/diacare.15.3.430. [DOI] [PubMed] [Google Scholar]
  8. DeFronzo R. A., Ferrannini E., Hendler R., Felig P., Wahren J. Regulation of splanchnic and peripheral glucose uptake by insulin and hyperglycemia in man. Diabetes. 1983 Jan;32(1):35–45. doi: 10.2337/diab.32.1.35. [DOI] [PubMed] [Google Scholar]
  9. DeFronzo R. A., Ferrannini E., Hendler R., Felig P., Wahren J. Regulation of splanchnic and peripheral glucose uptake by insulin and hyperglycemia in man. Diabetes. 1983 Jan;32(1):35–45. doi: 10.2337/diab.32.1.35. [DOI] [PubMed] [Google Scholar]
  10. DeFronzo R. A., Ferrannini E., Hendler R., Wahren J., Felig P. Influence of hyperinsulinemia, hyperglycemia, and the route of glucose administration on splanchnic glucose exchange. Proc Natl Acad Sci U S A. 1978 Oct;75(10):5173–5177. doi: 10.1073/pnas.75.10.5173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. DeFronzo R. A., Ferrannini E. Regulation of hepatic glucose metabolism in humans. Diabetes Metab Rev. 1987 Apr;3(2):415–459. doi: 10.1002/dmr.5610030204. [DOI] [PubMed] [Google Scholar]
  12. Desbuquois B., Aurbach G. D. Use of polyethylene glycol to separate free and antibody-bound peptide hormones in radioimmunoassays. J Clin Endocrinol Metab. 1971 Nov;33(5):732–738. doi: 10.1210/jcem-33-5-732. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Felig P., Wahren J., Hendler R. Influence of maturity-onset diabetes on splanchnic glucose balance after oral glucose ingestion. Diabetes. 1978 Feb;27(2):121–126. doi: 10.2337/diab.27.2.121. [DOI] [PubMed] [Google Scholar]
  15. Felig P., Wahren J., Hendler R. Influence of oral glucose ingestion on splanchnic glucose and gluconeogenic substrate metabolism in man. Diabetes. 1975 May;24(5):468–475. doi: 10.2337/diab.24.5.468. [DOI] [PubMed] [Google Scholar]
  16. Ferrannini E., Simonson D. C., Katz L. D., Reichard G., Jr, Bevilacqua S., Barrett E. J., Olsson M., DeFronzo R. A. The disposal of an oral glucose load in patients with non-insulin-dependent diabetes. Metabolism. 1988 Jan;37(1):79–85. doi: 10.1016/0026-0495(88)90033-9. [DOI] [PubMed] [Google Scholar]
  17. Ferrannini E., Wahren J., Felig P., DeFronzo R. A. The role of fractional glucose extraction in the regulation of splanchnic glucose metabolism in normal and diabetic man. Metabolism. 1980 Jan;29(1):28–35. doi: 10.1016/0026-0495(80)90094-3. [DOI] [PubMed] [Google Scholar]
  18. Gasic S., Kleinbloesem C. H., Heinz G., Waldhäusl W. Contribution of splanchnic and peripheral vascular tissues to the disposal of angiotensin-II and to regional conversion rates of angiotensin-I: a pilot study in humans. J Cardiovasc Pharmacol. 1991 Apr;17(4):615–620. doi: 10.1097/00005344-199104000-00014. [DOI] [PubMed] [Google Scholar]
  19. Horwitz D. L., Starr J. I., Mako M. E., Blackard W. G., Rubenstein A. H. Proinsulin, insulin, and C-peptide concentrations in human portal and peripheral blood. J Clin Invest. 1975 Jun;55(6):1278–1283. doi: 10.1172/JCI108047. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kelley D., Mitrakou A., Marsh H., Schwenk F., Benn J., Sonnenberg G., Arcangeli M., Aoki T., Sorensen J., Berger M. Skeletal muscle glycolysis, oxidation, and storage of an oral glucose load. J Clin Invest. 1988 May;81(5):1563–1571. doi: 10.1172/JCI113489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Molina J. M., Baron A. D., Edelman S. V., Brechtel G., Wallace P., Olefsky J. M. Use of a variable tracer infusion method to determine glucose turnover in humans. Am J Physiol. 1990 Jan;258(1 Pt 1):E16–E23. doi: 10.1152/ajpendo.1990.258.1.E16. [DOI] [PubMed] [Google Scholar]
  22. Myers S. R., McGuinness O. P., Neal D. W., Cherrington A. D. Intraportal glucose delivery alters the relationship between net hepatic glucose uptake and the insulin concentration. J Clin Invest. 1991 Mar;87(3):930–939. doi: 10.1172/JCI115100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Olefsky J. M., Kolterman O. G. Mechanisms of insulin resistance in obesity and noninsulin-dependent (type II) diabetes. Am J Med. 1981 Jan;70(1):151–168. doi: 10.1016/0002-9343(81)90422-8. [DOI] [PubMed] [Google Scholar]
  24. Olefsky J. M. LIlly lecture 1980. Insulin resistance and insulin action. An in vitro and in vivo perspective. Diabetes. 1981 Feb;30(2):148–162. doi: 10.2337/diab.30.2.148. [DOI] [PubMed] [Google Scholar]
  25. Pagliassotti M. J., Cherrington A. D. Regulation of net hepatic glucose uptake in vivo. Annu Rev Physiol. 1992;54:847–860. doi: 10.1146/annurev.ph.54.030192.004215. [DOI] [PubMed] [Google Scholar]
  26. Prager R., Wallace P., Olefsky J. M. In vivo kinetics of insulin action on peripheral glucose disposal and hepatic glucose output in normal and obese subjects. J Clin Invest. 1986 Aug;78(2):472–481. doi: 10.1172/JCI112599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. ROWELL L. B., BLACKMON J. R., BRUCE R. A. INDOCYANINE GREEN CLEARANCE AND ESTIMATED HEPATIC BLOOD FLOW DURING MILD TO MAXIMAL EXERCISE IN UPRIGHT MAN. J Clin Invest. 1964 Aug;43:1677–1690. doi: 10.1172/JCI105043. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Radziuk J., McDonald T. J., Rubenstein D., Dupre J. Initial splanchnic extraction of ingested glucose in normal man. Metabolism. 1978 Jun;27(6):657–669. doi: 10.1016/0026-0495(78)90003-3. [DOI] [PubMed] [Google Scholar]
  29. Radziuk J. Tracer methods and the metabolic disposal of a carbohydrate load in man. Diabetes Metab Rev. 1987 Jan;3(1):231–267. doi: 10.1002/dmr.5610030111. [DOI] [PubMed] [Google Scholar]
  30. Stoll R. W., Touber J. L., Menahan L. A., Williams R. H. Clearance of porcine insulin, proinsulin, and connecting peptide by the isolated rat liver. Proc Soc Exp Biol Med. 1970 Mar;133(3):894–896. doi: 10.3181/00379727-133-34589. [DOI] [PubMed] [Google Scholar]
  31. 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]

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