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 × kg1 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 amino acids(s). These data may be helpful in designing specific milk formulas with different effects on insulin and incretin response(s).