264-OR: Glucagon Kinetics: Model from First-in-Humans with 13C15N Glucagon

Abstract

We recently developed a novel stable glucagon tracer, [13C15N]-glucagon, to study glucagon kinetics and turnover in humans. Here, [13C15N]-glucagon was used to model glucagon kinetics during steady-state conditions in 5 nondiabetic subjects with complete data thus far (age 27±7 y; BMI 25.3±2.4 kg/m2, Mean±SD) who underwent two separate protocols: bolus injection (1497±564 pg/kg) and stop-from-constant infusion (138±33 pg/kg/min) of [13C15N]-glucagon. Arterialized blood was frequently sampled to measure the decay of [13C15N]-glucagon concentrations using tandem mass spectrometry. A linear, single compartment model was necessary and sufficient to reliably describe [13C15N]-glucagon kinetics and estimate both glucagon volume of distribution and clearance rate. The model well predicted the data (Fig. 1) and model parameters were estimated with precision (CV = 6±3 %). Volume of glucagon distribution was 37±9 mL/kg while clearance rate was 8.1±1.5 mL/kg/min. Results suggest that glucagon distributes in a single compartment with a volume of distribution approximately equal to the plasma volume. Additional nondiabetic and subjects with type 1 diabetes are currently under study. This model will be key to study postprandial glucagon turnover. Disclosure M. Schiavon: None. F. Ruchi: None. Y. R. Yadav: None. R. Basu: None. C. Cobelli: None. C. Dalla man: Research Support; Self; Becton, Dickinson and Company, Sanofi-Aventis Deutschland GmbH. A. Basu: None. Funding National Institutes of Health (DK085516 to A.B.), (DK029953 to R.B.); Italian Ministry of Education, University and Research (Law 232/2016 to M.S. and C.D.M.)