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Background: Milk protein, in particular the whey fraction, has been shown to display insulinotrophic properties in healthy persons and persons with type 2 diabetes. In parallel to the hyperinsulinemia, a pronounced postprandial rise of certain amino acids and of glucose-dependent insulinotrophic polypeptide (GIP) was observed in plasma. Objective: The objective of the study was to determine to what extent the insulinotrophic properties of whey could be simulated by specific amino acid mixtures. Design: Twelve healthy volunteers were served drinks consisting of pure glucose (reference drink) or glucose supplemented with free amino acids or whey proteins (test drinks). Results: A test drink with the branched-chain amino acids isoleucine, leucine, and valine resulted in significantly higher insulin responses than did the glucose reference. A drink containing glucose and leucine, isoleucine, valine, lysine, and threonine mimicked the glycemic and insulinemic responses seen after whey ingestion. With consumption of this drink, the glucose area under the curve (AUC) was 44% smaller (P < 0.05) and the insulin AUC was 31% larger (NS) than with consumption of the reference drink. With consumption of the whey drink, the AUCs were 56% smaller (glucose: P < 0.05) and 60% larger (insulin: P < 0.05), respectively, than with the reference drink. The whey drink was accompanied by an 80% greater GIP response (P < 0.05), whereas the drinks containing free amino acids did not significantly affect GIP secretion. Conclusion: A mixture of leucine, isoleucine, valine, lysine, and threonine resulted in glycemic and insulinemic responses closely mimicking those seen after whey ingestion in the absence of an additional effect of GIP and glucagon-like peptide 1. KEY WORDS Milk, whey, blood glucose, serum insulin, hyperinsulinemia, amino acids, incretin hormones

Background: Whey proteins have insulinotropic effects and reduce the postprandial glycemia in healthy subjects. The mechanism is not known, but insulinogenic amino acids and the incretin hormones seem to be involved. Objective: The aim was to evaluate whether supplementation of meals with a high glycemic index (GI) with whey proteins may increase insulin secretion and improve blood glucose control in type 2 diabetic subjects. Design: Fourteen diet-treated subjects with type 2 diabetes were served a high-GI breakfast (white bread) and subsequent high-GI lunch (mashed potatoes with meatballs). The breakfast and lunch meals were supplemented with whey on one day; whey was exchanged for lean ham and lactose on another day. Venous blood samples were drawn before and during 4 h after breakfast and 3 h after lunch for the measurement of blood glucose, serum insulin, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide 1 (GLP-1). Results: The insulin responses were higher after both breakfast (31%) and lunch (57%) when whey was included in the meal than when whey was not included. After lunch, the blood glucose response was significantly reduced [-21%; 120 min area under the curve (AUC)] after whey ingestion. Postprandial GIP responses were higher after whey ingestion, whereas no differences were found in GLP-1 between the reference and test meals. Conclusions: It can be concluded that the addition of whey to meals with rapidly digested and absorbed carbohydrates stimulates insulin release and reduces postprandial blood glucose excursion after a lunch meal consisting of mashed potatoes and meatballs in type 2 diabetic subjects. KEY WORDS Milk, whey, type 2 diabetes, blood glucose, serum insulin, incretin hormones

Background: Milk products deviate from other carbohydrate-containing foods in that they produce high insulin responses, despite their low GI. The insulinotropic mechanism of milk has not been elucidated. Objective: The objective was to evaluate the effect of common dietary sources of animal or vegetable proteins on concentrations of postprandial blood glucose, insulin, amino acids, and incretin hormones [glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1] in healthy subjects. Design: Twelve healthy volunteers were served test meals consisting of reconstituted milk, cheese, whey, cod, and wheat gluten with equivalent amounts of lactose. An equicarbohydrate load of white-wheat bread was used as a reference meal. Results: A correlation was found between postprandial insulin responses and early increments in plasma amino acids; the strongest correlations were seen for leucine, valine, lysine, and isoleucine. A correlation was also obtained between responses of insulin and GIP concentrations. Reconstituted milk powder and whey had substantially lower postprandial glucose areas under the curve (AUCs) than did the bread reference (-62% and -57%, respectively). Whey meal was accompanied by higher AUCs for insulin (90%) and GIP (54%). Conclusions: It can be concluded that food proteins differ in their capacity to stimulate insulin release, possibly by differently affecting the early release of incretin hormones and insulinotropic amino acids. Milk proteins have insulinotropic properties; the whey fraction contains the predominating insulin secretagogue. KEY WORDS Glycemic index, insulin index, milk, whey, food proteins, insulinotropic amino acids, amino acids, incretin hormones