Synergism by individual macronutrients explains the marked early GLP-1 and islet hormone responses to mixed meal challenge in mice

► We studied how macronutrients in combination affect glucose tolerance. ► A mixed meal significantly increased insulin secretion versus isocaloric glucose. ► This is partly due to synergism between macronutrients to stimulate GLP-1 release. ► Replacing part of glucose load with protein and fat thus improves β-cell function.