Effects of free fatty acid elevation on postabsorptive endogenous glucose production and gluconeogenesis in humans

Effects of free fatty acids (FFAs) on endogenous glucose production (EGP) a nd gluconeogenesis (GNG) were examined in healthy subjects (n = 6) during s tepwise increased Intralipid/heparin infusion (plasma FFAs 0.8 +/- 0.1, 1.8 +/- 0.2, and 2.8 +/- 0.3 mmol/l) and during glycerol infusion (plasma FFAs similar to 0.5 mmol/l), Rates of EGP were determined with D-[6,6-H-2(2)]gl ucose and contributions of GNG from H-2 enrichments in carbons 2 and 5 of b lood glucose after (H2O)-H-2 ingestion. Plasma glucose concentrations decre ased by similar to 10% (P <0.01), whereas plasma insulin increased by simil ar to 47% (P = 0.02) after 9 h of lipid infusion. EGP declined from 9.3 +/- 0.5 (Lipid) and 9.0 +/- 0.8 mu mol . kg(-1) . min(-1) (glycerol) to 8.4 +/ - 0.5 and 8.2 +/- 0.7 mu mol . kg(-1) . min(-1), respectively (P < 0.01), C ontribution of GNG similarly rose (P < 0.01) from 46 +/- 4 and 52 +/- 3% to 65 +/- 8 and 78 +/- 7%, To exclude interaction of FFAs with insulin secret ion, the study was repeated at fasting plasma insulin (similar to 35 pmol/l ) and glucagon (similar to 90 ng/ml) concentrations using somatostatin-insu lin-glucagon clamps. Plasma glucose increased by similar to 50% (P < 0.005) during lipid but decreased by similar to 12% during glycerol infusion (P < 0.005), EGP remained unchanged over the 9-h period (9.9 +/- 1.2 vs. 9.0 +/ - 1.1 mu mol . kg(-1) . min(-1)). GNG accounted for 62 +/- 5 (lipid) and 60 +/- 6% (glycerol) of EGP at time 0 and rose to 74 +/- 3% during lipid infu sion only (P < 0.05 vs. glycerol: 64 +/- 4%), In conclusion, high plasma FF A concentrations increase the percent contribution of GNG to EGP and may co ntribute to increased rates of GNG in patients with type 2 diabetes.