Postabsorptive Splanchnic And Leg Glucagon Metabolism In Healthy Subjects: Use Of 13c 15n Glucagon

Glucagon metabolism in humans is poorly understood and is currently under active investigation. We have recently developed a novel isotope dilution method using nonradioactive, stable human glucagon (Phe 6 13C9, 15N; Phe 22 13C9, 15N) tracer to measure glucagon turnover. In this study we combined this method with organ catheterization technique to estimate splanchnic and leg glucagon extraction and uptake. We present data from the first 6 healthy subjects (age 25±3.6 yrs; BMI 26.7±4.5 kg/m2; fasting glucose 4.6±0.5 mM; HbA1c 5.1±0.3%) completed thus far. After IRB approval and informed consent, subjects were admitted in the morning after an overnight fast to Interventional Radiology, where catheters were placed in the right femoral artery and vein under local anesthesia with aseptic precautions. Under fluoroscopic guidance, a hepatic venous catheter was positioned through the femoral vein. Glucagon tracer was infused intravenously and Indocyanine Green infused via the femoral artery sheath to measure splanchnic and femoral plasma flows. Plasma samples were collected periodically from femoral artery, femoral vein and hepatic vein for concentrations of glucagon tracer (Tandem Mass Spectrometry), glucagon, glucose and Indocyanine Green (Spectrophotometry) concentrations. Fractional splanchnic glucagon extraction was 24.0±12.5 % while total splanchnic glucagon uptake was 214.3±56.1 ng/kg total body weight/min. Net splanchnic glucagon balance was -34.4±10.0 ng/kg total body weight/min implying net splanchnic glucagon production. Fractional leg glucagon extraction was 13.5±3.8% while total leg glucagon uptake was 53.0±21.2 pg/kg total body weight/min. To the best of our knowledge, these initial data provide the first direct assessment of regional glucagon metabolism in healthy humans in the post absorptive fasting state. Disclosure F. Ruchi: None. Y.R. Yadav: None. D. Romeres: None. S. Sawleh: None. L.M. Benson: None. K.L. Johnson: None. C. Dalla Man: Research Support; Self; Sanofi-Aventis Deutschland GmbH. C. Cobelli: None. D.J. McCormick: None. L.R. Wilkins: None. R. Basu: Consultant; Self; GENFIT. Research Support; Self; AstraZeneca. A. Basu: Consultant; Spouse/Partner; GENFIT. Research Support; Spouse/Partner; AstraZeneca. Funding National Institutes of Health (R01DK029953 to R.B.), (R01DK085516 to A.B.), (DK059637, DK020593)