1916-P: Postprandial Glucagon Metabolism in Healthy Subjects: Use of 13C 15N Glucagon

• Published in: Diabetes (New York, N.Y.) Vol. 69; no. Supplement_1
• Main Authors: RUCHI, FNU, YADAV, YOGESH R., ROMERES, DAVIDE, SAWLEH, SAFIA, BENSON, LINDA M., JOHNSON, KENNETH L., SCHIAVON, MICHELE, MAN, CHIARA DALLA, COBELLI, CLAUDIO, MCCORMICK, DANIEL J., BASU, RITA, BASU, ANANDA
• Format: Journal Article
• Language: English
• Published: New York American Diabetes Association 01.06.2020
• Subjects: Catheters; Diabetes; Forearm; Glucagon; Isotope dilution method; Mass spectroscopy; Metabolism
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db20-1916-P

Glucagon metabolism in humans is poorly understood and is currently under active investigation. We have recently developed a new isotope dilution method using nonradioactive, stable human glucagon (Phe 6 13C9, 15N; Phe 22 13C9, 15N) tracer to measure glucagon fluxes. To estimate postprandial glucagon turnover using this novel technique, we present data from the first 5 healthy subjects (3 males, age 26.2±7.9 years, BMI 25.4±2.6 kg/m2, fasting plasma glucose 4.7±0.2 mM, HbA1c 5.1±0.2 %) done thus far. After IRB approval and informed consent, subjects presented to the clinical research unit in the morning after an overnight fast. A catheter was inserted in a forearm vein for glucagon tracer infusion and another catheter placed in the contralateral hand and the hand kept in a heated box for periodic draws of arterialized venous samples for measurements of glucagon tracer (tandem mass spectrometry), glucagon and glucose concentrations during the study. A mixed meal (75 grams carb, 15% protein, 35% fat; 8 kcal/kg) was ingested at time 0 and the glucagon tracer infusion rate adjusted to mimic the anticipated changes in postprandial circulating glucagon concentrations for 6 hours. Systemic glucagon appearance rate (Ra glucagon) was calculated by the isotope dilution method. Fig 1 shows the Ra glucagon in all subjects. These initial data show that postprandial glucagon turnover can be calculated in humans applying this novel technique.