Glucagon regulates its own secretion indirectly by stimulating β-cells to secrete insulin. This may serve as a compensatory mechanism to enhance β-cell function in individuals with, or predisposed to, type 2 diabetes (T2D). However, tools to quantify glucagon-induced C-peptide secretion rate (SR) are lacking. To bridge this gap, we developed a novel model-based method to provide quantitative indices of β-cell function in response to a glucagon bolus in individuals without and with type 2 diabetes. Eight individuals without diabetes [3 M, age = 55 ± 9 yr, body mass index (BMI) = 32 ± 4 kg/m