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The 75-g oral glucose tolerance test: Effect on splanchnic metabolism of substrates and pancreatic hormone release in healthy man


To determine the effect of the 75 g oral glucose tolerance test on carbohydrate and lipid metabolism, the splanchnic exchange of glucose, lactate, pyruvate, non-esterified fatty acids, β- hydroxybutyrate and acetoacetate as well as the release of insulin, C-peptide, glucagon and pancreatic polypeptide were evaluated in eight healthy male volunteers in the basal state and for 150 min following glucose ingestion. Oral glucose loading was followed by a rapid rise in splanchnic output of glucose (mean±SEM; 154±12 mmol/150 min), pyruvate (1.2±1.2 mmol/150 min) and lactate (8.6±2.0 mmol/150 min), whereas there were reductions in the splanchnic uptake of non-esterified fatty acids (-10.7±4.4 mmol/150 min) and the splanchnic output of β-hydroxybutyrate (-4.8±3.3 mmol/150 min) and acetoacetate (-3.0±1.2 mmol/150 min). In parallel, splanchnic output of insulin (12.3±2.7 nmol/150 min), C-peptide (36.1±5.0 nmol/ 150 min) and transiently of pancreatic polypeptide rose, whereas that of glucagon fell (-0.58±0.21 nmol/150 min). Even at 150 min after glucose ingestion, splanchnic ouptut and arterial concentrations of glucose, lactate, insulin and C-peptide were still above their respective basal values while those of non-esterified fatty acids and glucagon were reduced. Taking into account the partial suppression of endogenous glucose production by ingested glucose it is concluded that, in normal postabsortive man, only 49–63% of a 75 g oral glucose load is retained by the splanchnic bed during the first 150 min, the rest being available for non-hepatic tissues. Since typical metabolic responses to oral glucose loading were maintained up to 150 min after glucose ingestion, it appears that glucose absorption from the gut was not yet complete within this time. This finding partially jeopardizes the interpretation of calculated post-prandial hepatic glucose uptake for short observation periods.


  1. 1.

    Waldhäusl W, Bratusch-Marrain P, Gasić S, Korn A, Nowotny P (1979) Insulin production rate following glucose ingestion estimated by splanchnic C-peptide output in normal man. Diabetologia 17: 221–227

  2. 2.

    Bratusch-Marrain P, Waldhäusl WK, Gasić S, Korn A, Nowotny P (1980) Oral glucose tolerance test: effect of different glucose loads on splanchnic carbohydrate and substrate metabolism in healthy men. Metabolism 29: 289–295

  3. 3.

    Felig P, Wahren J, Hendler R (1975) Influence of oral glucose ingestion on splanchnic glucose and gluconeogenic substrate metabolism in man. Diabetes 24: 468–475

  4. 4.

    WHO (1980) Expert Committee on Diabetes Mellitus. World Health Organisation Technical Report Series 646. World Health Organisation, Geneva

  5. 5.

    Rabinowitz D, Liljenquist JE (1978) Glucose metabolism in intact man: the responsiveness of splanchnic and peripheral tissues to insulin. Metabolism 27: 1832–1838

  6. 6.

    Madison LL (1969) Role of insulin in hepatic handling of glucose. Arch Int Med 123: 284–292

  7. 7.

    Rowell LB, Blackmon JR, Bruce RA (1964) Indocyanine clearance and estimated hepatic blood flow during mild to maximal exercise in upright man. J Clin Invest 43: 1677–1690

  8. 8.

    Bradley SE, Ingelfinger EJ, Bradley GP, Curry JJ (1945) The estimation of hepatic blood flow in man. J Clin Invest 24: 890–897

  9. 9.

    Paschen U, Müller MJ, Seitz HJ (1981) Indocyanine green liver blood flow measurement in the pig. J Clin Chem Clin Biochem 19: 797 (Abstract)

  10. 10.

    Bergmeyer HU (ed) (1974) Methoden der enzymatischen Analyse. Verlag Chemie, Weinheim

  11. 11.

    Waldhäusl W, Haydl H, Nowotny P (1976) ACTH and cortisol responses to glucagon stimulation. J Clin Endocrinol Metab 43: 675–678

  12. 12.

    Waldhäusl W, Kleinberger G, Korn A, Dudczak R, Bratusch-Marrain P, Nowotny P (1979) Severe hyperglycemia: effects of rehydration on endocrine derangements and blood glucose concentrations. Diabetes 28: 577–584

  13. 13.

    Zahn H, Klostermeyer H (1969) Die Inselzellhormone: Chemie, Struktur und Synthese von Insulin. In: Pfeiffer EF (ed) Handbook of diabetes mellitus, Vol 2. Lehmanns, München, pp 118–147

  14. 14.

    Oyer PE, Cho S, Patterson JD, Steiner DF (1971) Studies on human proinsulin. Isolation and amino acid sequence of human pancreatic C-peptide. J Biol Chem 246: 1375–1386

  15. 15.

    Bromer WW, Sinn LG, Behrens OK (1957) The amino acid sequence of glucagon. V. Location of amide groups, acid degradation studies and summary of sequential analysis. J Am Chem Soc 79: 2807–2810

  16. 16.

    Floyd JC Jr, Fajans SS, Pek S, Chance RE (1977) A newly recognized pancreatic polypeptide; plasma levels in health and disease. Rec Progr Horm Res 33: 519–570

  17. 17.

    Waldhäusl W, Bratusch-Marrain P, Gasić S, Korn A, Nowotny P (1982) Insulin production rate, hepatic insulin retention and splanchnic carbohydrate metabolism after oral glucose ingestion in hyperinsulinaemic Type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 23: 6–15

  18. 18.

    Bratusch-Marrain P, Waldhäusl W, Gasić S, Hofer A (1983) Hepatic disposal of biosynthetic human insulin and porcine C-peptide in man. Metabolism (in press)

  19. 19.

    Waldhäusl W, Gasić S, Bratusch-Marrain P, Korn A, Nowotny P (1982) Action of biosynthetic human insulin on endogenous insulin release and hepatic insulin disposal in healthy man. Am J Physiol 243: 476–482

  20. 20.

    Statistik (1968) In: Dien K, Lentner C (eds) Dokumenta Geigy, 7th ed. Ciba-Geigy, Basel, pp 146–199

  21. 21.

    Bratusch-Marrain P, Korn A, Waldhäusl WK, Gasić S, Nowotny P (1981) Effect of buformin on splanchnic carbohydrate and substrate metabolism in healthy man. Metabolism 30: 946–952

  22. 22.

    Radziuk J, McDonald TJ, Rubenstein D, Dupre J (1978) Initial splanchnic extraction of ingested glucose in normal man. Metabolism 27: 657–669

  23. 23.

    Jacot E, DeFronzo RA, Jequier E, Maeder E, Felber JP (1982) The effect of hyperglycemia, hyperinsulinemia and route of glucose administration on glucose oxidation and storage. Metabolism 31: 922–930

  24. 24.

    Ferrannini E, Wahren J, Felig P, DeFronzo RA (1980) The role of fractional glucose extraction in the regulation of splanchnic glucose metabolism in normal and diabetic man. Metabolism 29: 28–35

  25. 25.

    Felig P, Wahren J, Hendler R (1978) Influence of maturity onset diabetes on splanchnic glucose balance after oral glucose ingestion. Diabetes 27: 121–126

  26. 26.

    Domstad PA, Kim EE, Coupal JJ, Beihn R, Yonts S, Choy YC, Mandelstam P, DeLand FH (1980) Biologic gastric emptying time in diabetic patients, using Tc — 99m — labelled resin oat meal with and without metoclopramide. J Nucl Med 21: 1098–1100

  27. 27.

    Cahill GF, Herrera MG, Morgan AP, Soeldner JS, Steincke J, Levy PL, Reichard GA, Kipnis DM (1966) Hormone fuel interrelationships during fasting. J Clin Invest 45: 1751–1769

  28. 28.

    Perley MJ, Kipnis DM (1967) Plasma insulin responses to oral and intravenous glucose: studies in normal and diabetic subjects. J Clin Invest 46: 1954–1962

  29. 29.

    Scow RL, Cornfield J (1954) Quantitative relation between oral and intravenous glucose tolerance curves. Am J Physiol 179: 435–438

  30. 30.

    Felig P, Wahren J (1971) Influence of endogenous insulin secretion on splanchnic glucose and amino acid metabolism in man. J Clin Invest 50: 1702–1711

  31. 31.

    Steele R, Bishop JS, Altszuler N, Rathgeb I, DeBodo RC (1965) Inhibition by insulin of hepatic glucose production in the normal dog. Am J Physiol 208: 301–306

  32. 32.

    Bergmann RN (1977) Integrated control of hepatic glucose metabolism. Federation Proc 36: 265–270 (1977)

  33. 33.

    Huckabee WE (1958) Relationship of pyruvate and lactate during anaerobic metabolism. I. Effects of infusion of pyruvate, glucose and of hyperventilation. J Clin Invest 37: 244–254

  34. 34.

    Doar JWH, Cramp DG, Maw DSI, Seed M, Wynn V (1970) Blood pyruvate and lactate levels during oral and intravenous glucose tolerance tests in diabetes mellitus. Clin Sci 39: 259–269

  35. 35.

    Sussman KE (1966) Effect of prolonged fasting on glucose and insulin metabolism in exogenous obesity. Arch Int Med 117: 343–347

  36. 36.

    Jackson RA, Peters N, Advani U, Perry G, Rogers J, Brough WH, Pilkington TRE (1973) Forearm glucose uptake during the oral glucose tolerance test in normal subjects. Diabetes 22: 442–458

  37. 37.

    Basso LV, Havel RJ (1970) Hepatic metabolism of free fatty acids in normal and diabetic dogs. J Clin Invest 49: 537–547

  38. 38.

    McCarry JE, Foster DW (1977) Hormonal control of ketogenesis. Biochemical considerations. Arch Intern Med 137: 495–501

  39. 39.

    Ball EG, Jungas RL (1963) Studies on the metabolism of adipose tissue. XIII. The effect of anaerobic conditions and dietary regime on the response to insulin and epinephrine. Biochemistry 2: 586–592

  40. 40.

    Foster DW (1967) Studies on the ketosis of fasting. J Clin Invest 46: 1283–1296

  41. 41.

    Owen OW, Reichard GA Jr (1971) Human forearm metabolism during progressive starvation. J Clin Invest 50: 1536–1545

  42. 42.

    Sherwin RS, Kramer KJ, Tobin JD, Insel PA, Liljenquist JE, Berman M, Andres R (1974) A model of the kinetics of insulin man. J Clin Invest 53: 1481–1492

  43. 43.

    Mondon CE, Olefsky JM, Dolkas CB, Reaven GM (1975) Removal of insulin by perfused rat liver: effect of concentration. Metabolism 24: 153–160

  44. 44.

    Harding PE, Bloom G, Field JB (1975) Effect of infusion of insulin into portal vein on hepatic extraction of insulin in anesthetized dogs. Am J Physiol 228: 1580–1588

  45. 45.

    Unger RH, Aguilar-Parada E, Müller WA, Eisentraut AM (1970) Studies of pancreatic alpha cell function in normal and diabetic subjects. J Clin Invest 49: 837–848

  46. 46.

    Fisher M, Sherwin RS, Hendler R, Felig P (1976) Kinetics of glucagon in man: effects of starvation. Proc Natl Acad Sci USA 73: 1735–1739

  47. 47.

    Liljenquist JE, Rabin D (1979) Lack of a role of glucagon in the disposal of an oral glucose load in normal man. J Clin Endocrinol Metab 49: 937–939

  48. 48.

    Bratusch-Marrain P, Waldhäusl W, Grubeck-Loebenstein B, Korn A, Vierhapper H, Nowotny P (1981) The role of diabetogenic hormones on carbohydrate and lipid metabolism following oral glucose loading in insulin dependent diabetics: effects of acute hormone administration. Diabetologia 21: 387–393

  49. 49.

    Williamson JR (1967) Effects of fatty acids, glucagon and anti-insulin serum on the control of gluconeogenesis and ketogenesis in rat liver. Adv Enzyme Reg 5: 229–255

  50. 50.

    Lefebvre P (1977) Glucagon and lipid metabolism. In: Lefebvre PJ, Unger RH (eds) Glucagon: molecular physiology, clinical and therapeutic implications. Pergamon Press, Oxford, pp 109–121

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Waldhäusl, W.K., Gasić, S., Bratusch-Marrain, P. et al. The 75-g oral glucose tolerance test: Effect on splanchnic metabolism of substrates and pancreatic hormone release in healthy man. Diabetologia 25, 489–495 (1983).

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Key words

  • Standard oral glucose tolerance test
  • splanchnic glucose output
  • splanchnic glucose retention
  • insulin production rate
  • non-esterified fatty acids
  • glucagon
  • pancreatic polypeptide