Effect of Reversal of Whey‐Protein to Casein Ratio of Cow Milk, on Insulin, Incretin, and Amino Acid Responses in Humans

SCOPE: Milk‐proteins, besides lactose, stimulate insulin and incretin secretion. Although whey‐proteins (WP) are more efficient than casein (Cas) in hormone secretion, the effects of reversal of the (WP/Cas) ratio in whole‐milk are poorly known. METHODS AND RESULTS: Healthy volunteers received two different cow‐milk drinks, at identical lactose (0.36 g × kg(−1) BW) and total‐protein (0.18 g × kg(1) BW) loads, but at reversed WP/Cas ratio. One is cow‐whole milk with a ≈20/80 [WP/Cas] ratio, the other an experimental cow‐milk with a ≈70/30 [WP/Cas] ratio ([↑WP↓Cas]‐milk). Both milk‐types induced the same mild hyperglycemic response. Following [↑WP↓Cas]‐milk, the [20′–90′] insulin incremental area (iAUC) (+ ≈44%, p < 0.035), and the [20′–120′] C‐peptide iAUC (+ ≈47%, p < 0.015) are greater than those with cow‐milk. Similarly, following [↑WP↓Cas]‐milk, the GLP‐1 [20′–90′] iAUC (+96%, p < 0.025), and the GIP [30′–60′] iAUC (+140%, p < 0.006), were greater than those with cow‐milk. Plasma total and branched‐chain amino acids are also greater following the [↑WP↓Cas] than cow‐milk. CONCLUSIONS: Reversal of the (WP/Cas) ratio in cow‐milk enhanced the insulin response, an effect possibly mediated by incretins and/or amino acids(s). These data may be useful in designing specific milk formulas with different effects on insulin and incretin response(s).