Glucagon (Gn) stimulates insulin secretion. However, tools to quantify β-cell responsivity to Gn are lacking. We therefore developed a novel method that provides quantitative indexes of β-cell function in response to a Gn bolus in people without (ND) and with type 2 diabetes (T2D).Eight ND individuals (3M, age = 55±9 yrs, BMI = 32±4 kg/m2) and 6 with T2D (1M, age = 59±5 yrs, BMI = 35±6 kg/m2) underwent a 210-min hyperglycemic clamp (~9 mmol/L). After 180 min, a 1 mg bolus of Gn was administered over 1 min and plasma Gn and C-peptide concentrations were frequently measured over 30 min. After testing a battery of mathematical models describing Gn-stimulated C-peptide secretion (CS), we selected one that assumes that CS is made up of two components, one proportional to the above basal Gn, through parameter Γs (static), and one proportional to Gn rate of change, through parameter Γd (dynamic responsivity to Gn). An index of total β-cell responsivity to Gn (Γtot) can also be calculated from Γs andΓd.Model estimated Γs, Γd, and Γtot were significantly lower in T2D compared to ND (p<0.05), as shown in Fig. 1.
In conclusion, our findings reveal notable differences in both static, dynamic and total insulin secretory response between individuals with and without T2D, demonstrating that decreased β-cell responsiveness in T2D includes impaired responses to Gn as well as glucose.
F. Boscolo: None. E. Faggionato: None. A. Vella: Research Support; Novo Nordisk. Consultant; Hanmi Pharm. Co., Ltd., Crinetics Pharmaceuticals, Inc. Advisory Panel; Rezolute, Inc. C. Dalla Man: None.
