Amino Acids

, Volume 37, Issue 2, pp 333–339 | Cite as

Human insulinotropic response to oral ingestion of native and hydrolysed whey protein

  • O. PowerEmail author
  • A. Hallihan
  • P. Jakeman
Original Article


The insulinotropic response to the ingestion of whey protein and whey protein hydrolysate, independent of carbohydrate, is not known. This study examined the effect of protein hydrolysis on the insulinotropic response to the ingestion of whey protein. Sixteen healthy males ingested a 500 mL solution containing either 45 g of whey protein (WPI) or whey protein hydrolysate (WPH). The estimated rate of gastric empting was not altered by hydrolysis of the protein [18 (3) vs. 23 (3) min, n = 16; P = 0.15]. Maximum plasma insulin concentration (C max) occurred later (40 vs. 60 min) and was 28% [234 (26) vs. 299 (31) mM, P = 0.018] greater following ingestion of the WPH compared to the WPI leading to a 43% increase [7.6 (0.9) vs. 10.8 (2.6) nM, P = 0.21] in the AUC of insulin for the WPH. Of the amino acids with known insulinotropic properties only Phe demonstrated a significantly greater maximal concentration [C max; 65 (2) vs. 72 (3) μM, n = 16; P = 0.01] and increase (+22%) in AUC following ingestion of the WPH. In conclusion, ingestion of whey protein is an effective insulin secretagogue. Hydrolysis of whey protein prior to ingestion augments the maximal insulin concentration by a mechanism that is unrelated to gastric emptying of the peptide solution.


Amino acids Insulin Whey protein Peptide hydrolysate Gastric emptying 



Amino acid


Essential amino acid














Branched chain amino acids


Gastric emptying


Whey proteins isolate


Whey protein hydrolysate


Reverse phase high performance liquid chromatography


Area under the curve


Half-time of gastric emptying


Time of maximum plasma concentration


Maximum plasma concentration


Glucose dependent insulinotropic polypeptide


Glucagon-like-peptide 1



The authors acknowledge the financial support of Enterprise Ireland (Grant IP 2004-237) and Carbery Food Ingredients.


  1. Bennet WM, Connacher AA, Scrimgeour CM, Jung RT, Rennie MJ (1990) Euglycemic hyperinsulinemia augments amino acid uptake by human leg tissues during hyperaminoacidemia. Am J Phy Endocrinol Metab 259:E185–E194Google Scholar
  2. Bland MJ, Altman DG (1986) Statistical methods for assessing agreement between two methods of clinical measurement 1:307–310Google Scholar
  3. Calbet JAL, Maclean DA (2002) Plasma glucagon and insulin responses depend on the rate of appearance of amino acids after ingestion of different protein solutions in humans. Eur J Nutr 132:2174–2182Google Scholar
  4. Calbet JA, Holst JJ (2004) Gastric emptying, gastric secretion and enterogasterone response after administration of milk proteins or their peptide hydrolysates in humans. Eur J Nutr 43:127–139PubMedCrossRefGoogle Scholar
  5. Claessens M, Saris WHM, Baak MAV (2008) Glucagon and insulin responses after ingestion of different amounts of intact and hydrolysed proteins. Br J Nutr 100:61–69PubMedCrossRefGoogle Scholar
  6. Clements J, Heading R, Nimmo W, Prescott L (1978) Kinetics of acetaminophen absorption and gastric emptying in man. Clin Pharm Ther 24:420–432Google Scholar
  7. Dorresteijn RC, Berwald LG, Zomer G, Goijer CDD (1996) Determination of amino acids using o-phthaldehyde–2-mercaptoethanol derivatisation effect of reaction conditions. J Chrom A 724:159–167CrossRefGoogle Scholar
  8. Floyd J, Fajans S, Conn J, Rull J (1966) Stimulation of insulin secretion by amino acids. J Clin Invest 45:1487–1502PubMedCrossRefGoogle Scholar
  9. Floyd J, Fajans S, Pek S, Thiffault CA, Knopf R (1970) Synergistic effect of essential amino acids and glucose upon insulin secretion in man. Diabetes 19:109–115PubMedGoogle Scholar
  10. Frid AH, Nilsson M, Holst JJ, Bjorck IME (2005) Effect of whey on blood glucose and insulin responses to composite breakfast and lunch meals in type 2 diabetic subjects. Am J Clin Nutr 82:69–75PubMedGoogle Scholar
  11. Gotelli G, Kabra PM, Marton LJ (1977) Determination of acetaminophen and phenacetin in plasma by high-pressure liquid chromatography. Clin Chem 23:957–959PubMedGoogle Scholar
  12. Halton TL, Hu FB (2004) The effects of high protein diets on thermogenesis, satiety and weight loss: a critical review. J Am Coll Nutr 23:373–385PubMedGoogle Scholar
  13. Holst JJ, Gromada J (2004) Role of incretin hormones in the regulation of insulin secretion in diabetic and nondiabetic humans. Am J Physiol Endocrinol Metab 287:E199–E206PubMedCrossRefGoogle Scholar
  14. Holt S, Miller JB, Petocz P (1996) Interrelationships among postprandial satiety, glucose and insulin responses and changes in subsquest food intake. Eur J Clin Nutr 50:788–797PubMedGoogle Scholar
  15. Manders RJF, Wagenmakers AJM, Koopman R, Zorenc AHG, Menheere PPCA, Schaper NC, Saris WHM, Van Loon LJC (2006) Co-ingestion of a protein hydrolysate and amino acid mixture with carbohydrate improves plasma glucose disposal in patients with type 2 diabetes. Am J Clin Nutr 82:76–83Google Scholar
  16. Medhus AW, Sandstad O, Bredesen J, Husebye E (1999) Delay of gastric emptying by duodenal intubation: sensitive measurement of gastric emptying by the paracetamol absorption test. Ali Phar Ther 13:609–620CrossRefGoogle Scholar
  17. Naslund E, Bogefors J, Gryback P, Jacobsson H, Hellstrom PM (2000) Gastric emptying: comparison of scintigraphic, polyethylene glycol dilution and paracetamol tracer assessment technique. Scand J Gastroenterol 35:375–378PubMedCrossRefGoogle Scholar
  18. Newsholme P, Bender K, Kiely A, Brennan L (2007) Amino acid metabolism, insulin secretion and diabetes. Biochemical Soc Trans 35:1180–1187CrossRefGoogle Scholar
  19. Nilsson M, Holst JJ, Bjorck IME (2007) Metabolic effects of amino acid mixtures and whey protein in healthy subjects: studies using glucose-equivalent drinks. Am J Clin Nutr 85:996–1004PubMedGoogle Scholar
  20. Price C, Hammond P, Scawen MD (1983) Evaluation of an enzymatic procedure for measurement of acetaminophen. Clin Chem 29:358–361PubMedGoogle Scholar
  21. Schmid R, Schulte-Forhlinde E, Schusdziarra V, Stegmann J, Maier V, Classen M (1992) Contribution of postprandial amino acid levels to stimulation of insulin, glucagon and pancreatic polypeptide in humans. Pancreas 7:698–704PubMedCrossRefGoogle Scholar
  22. Turnell DC, Cooper JDH (1982) Rapid assay for amino acids in serum or urine by pre-column derivatisation and reversed-phase liquid chromatography. Clin Chem 28:527–531PubMedGoogle Scholar
  23. Van Loon LJ, Saris W, Verhagen H, Wagenmakers A (2000) Plasma insulin response after ingestion of different amino acid or protein mixtures with carbohydrate. Am J Clin Nutr 72:96–105PubMedGoogle Scholar
  24. Wahren J, Felig P, Hagenfeldt L (1976) Effect of protein ingestion on splanchnic and leg metabolism in normal man and in patients with diabetes mellitus. J Clin Invest 57:987–999PubMedCrossRefGoogle Scholar
  25. Wolfe RR (2006) The underappreciated role of muscle in health and disease. Am J Clin Nutr 84:475–482PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  1. 1.Human Science Research Unit, Department of Physical Education and Sports ScienceUniversity of LimerickLimerickIreland
  2. 2.Carbery Food IngredientsBallineenIreland

Personalised recommendations