Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1997 Nov 1;100(9):2354–2361. doi: 10.1172/JCI119775

Evidence for decreased splanchnic glucose uptake after oral glucose administration in non-insulin-dependent diabetes mellitus.

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: PMC508433  PMID: 9410915

Abstract

The role of splanchnic glucose uptake (SGU) after oral glucose administration as a potential factor contributing to postprandial hyperglycemia in non-insulin-dependent diabetes mellitus (NIDDM) has not been established conclusively. Therefore, we investigated SGU in six patients with NIDDM and six weight-matched control subjects by means of the hepatic vein catheterization (HVC) technique. In a second part, we examined the applicability of the recently developed OG-CLAMP technique in NIDDM by comparing SGU and first-pass SGU during HVC with SGU during the OG-CLAMP experiment. The OG-CLAMP method combines a euglycemic, hyperinsulinemic clamp and an oral glucose tolerance test (75 g) during steady state glucose infusion (GINF). During HVC, SGU equals the splanchnic fractional extraction times the total (oral and arterial) glucose load presented to the liver. For OG-CLAMP, SGU was calculated as first-pass SGU by subtracting the integrated decrease in GINF over 180 min from 75 g. Cumulative splanchnic glucose output after oral glucose correlated significantly between both methods and was increased significantly in NIDDM patients (73.1+/-5.1 g for HVC, 76.5+/-5.5 for OG-CLAMP) compared with nondiabetic patients (46.7+/-4.4 g for HVC, 57.5+/-1.9 for OG-CLAMP). Thus, in NIDDM patients, SGU (7.4+/-2.1 vs. 37.8+/-5.9% in nondiabetic patients, P < 0.001) and first-pass SGU (4.7+/-1.7 vs. 26.5+/-5.1% in nondiabetic patients, P < 0.01) were decreased significantly during HVC, as was SGU during OG-CLAMP (3.9+/-1.7 vs. 23.4+/-2.5% in nondiabetic patients, P < 0.0001). SGU measured during OG-CLAMP correlated significantly with SGU (r = 0.87, P < 0.05 for NIDDM patients; r = 0.94, P < 0.01 for nondiabetic patients) and first-pass SGU (r = 0.87, P < 0.05 for NIDDM patients; r = 0.84, P < 0.05 for nondiabetic patients) during HVC. In conclusion, (a) SGU after oral glucose administration is decreased in NIDDM as measured by both methods, and (b) SGU during the OG-CLAMP is well-correlated to SGU and first-pass SGU during HVC in NIDDM. The decrease in SGU in NIDDM might contribute to postprandial hyperglycemia in diabetic subjects.

Full Text

The Full Text of this article is available as a PDF (235.4 KB).

Selected References

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

  1. Bergman R. N., Finegood D. T., Ader M. Assessment of insulin sensitivity in vivo. Endocr Rev. 1985 Winter;6(1):45–86. doi: 10.1210/edrv-6-1-45. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. 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]
  4. 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]
  5. 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]
  6. DeFronzo R. A. Lilly lecture 1987. The triumvirate: beta-cell, muscle, liver. A collusion responsible for NIDDM. Diabetes. 1988 Jun;37(6):667–687. doi: 10.2337/diab.37.6.667. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. 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]
  9. 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]
  10. 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]
  11. 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]
  12. 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]
  13. Firth R. G., Bell P. M., Marsh H. M., Hansen I., Rizza R. A. Postprandial hyperglycemia in patients with noninsulin-dependent diabetes mellitus. Role of hepatic and extrahepatic tissues. J Clin Invest. 1986 May;77(5):1525–1532. doi: 10.1172/JCI112467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. Ludvik B., Nolan J. J., Roberts A., Baloga J., Joyce M., Bell J. M., Olefsky J. M. A noninvasive method to measure splanchnic glucose uptake after oral glucose administration. J Clin Invest. 1995 May;95(5):2232–2238. doi: 10.1172/JCI117913. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Magnusson I., Rothman D. L., Katz L. D., Shulman R. G., Shulman G. I. Increased rate of gluconeogenesis in type II diabetes mellitus. A 13C nuclear magnetic resonance study. J Clin Invest. 1992 Oct;90(4):1323–1327. doi: 10.1172/JCI115997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Mitrakou A., Kelley D., Veneman T., Jenssen T., Pangburn T., Reilly J., Gerich J. Contribution of abnormal muscle and liver glucose metabolism to postprandial hyperglycemia in NIDDM. Diabetes. 1990 Nov;39(11):1381–1390. doi: 10.2337/diab.39.11.1381. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. 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]
  20. 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]
  21. 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]
  22. 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]
  23. 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]
  24. 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]

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

RESOURCES