1707-P: Differential Effect of Prolonged Glucagon Infusion on Plasma Lipidome in Humans

Hyperglucagonemia plays an important role in pathogenesis of T2DM. The effect of glucagon on the plasma lipidome has not been studied in humans. We examined the effect of prolonged glucagon infusion on plasma lipid metabolites in healthy subjects. 8 NGT subjects (5M/3F, age=35±5, BMI=24±1, A1c=5.3±0.3%) received 12-hour (6PM to 6AM) glucagon infusion (6ng/kg/min). On a different day the subjects returned for a repeat study with infusion (6PM to 6AM) of normal saline. Top-ranking plasma lipidomes were measured by shotgun lipidomics including Phosphatidylethanolamine (PE), Lysophosphatidylethanolamine (LPE), Phosphatidylcholine (PC), Lysophosphatidylcholine (LPC), Ceramide (CER), Sphingomyelin (SM), Acylcarnitine (AC), Phosphatidylglycerol (PG), Phosphatidylinositol (PI), Phosphatidylserine (PS), Triacylglycerol (TAG), Fatty Acyl Chains in TAG (FA). Plasma glucagon increased from 57±3 to 219±21 pg/ml. Plasma insulin increased significantly following glucagon compared to saline (20±7 vs. 8±3 mU/L, p In conclusion, prolonged glucagon infusion modulates novel lipid metabolites involved in inflammation and represents a fundamental mechanism by which glucagon activates inflammation pathways, contributing to insulin resistance. Disclosure X. Chen: None. X. Han: None. J. Trejo: None. E. Case: None. R.A. DeFronzo: None. D. Tripathy: None. Funding Foundation for Advancement of Veteran’s Health and Research