title: Effects of free fatty acid elevation on postabsorptive endogenous glucose production and gluconeogenesis in humans.
abstract: Effects of free fatty acids (FFAs) on endogenous glucose production (EGP) and gluconeogenesis (GNG) were examined in healthy subjects (n = 6) during stepwise 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 approximately 0.5 mmol/l). Rates of EGP were determined with D-[6,6-2H2]glucose and contributions of GNG from 2H enrichments in carbons 2 and 5 of blood glucose after 2H2O ingestion. Plasma glucose concentrations decreased by approximately 10% (P < 0.01), whereas plasma insulin increased by approximately 47% (P = 0.02) after 9 h of lipid infusion. EGP declined from 9.3+/-0.5 (lipid) and 9.0+/-0.8 pmol x kg(-1) x min(-1) (glycerol) to 8.4+/-0.5 and 8.2+/-0.7 micromol x kg(-1) x min(-1), respectively (P < 0.01). Contribution 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 secretion, the study was repeated at fasting plasma insulin (approximately 35 pmol/l) and glucagon (approximately 90 ng/ml) concentrations using somatostatin-insulin-glucagon clamps. Plasma glucose increased by approximately 50% (P < 0.005) during lipid but decreased by approximately 12% during glycerol infusion (P < 0.005). EGP remained unchanged over the 9-h period (9.9+/-1.2 vs. 9.0+/-1.1 micromol x kg(-1) x min(-1)). GNG accounted for 62+/-5 (lipid) and 60+/-6% (glycerol) of EGP at time 0 and rose to 74+/-3% during lipid infusion only (P < 0.05 vs. glycerol: 64+/-4%). In conclusion, high plasma FFA concentrations increase the percent contribution of GNG to EGP and may contribute to increased rates of GNG in patients with type 2 diabetes.
authors.affiliation: Department of Internal Medicine III, University of Vienna Medical School, Austria. michael.roden@akh-wien.ac.at
authors.forename: M
authors.initials: M
authors.lastname: Roden
authors.forename: H
authors.initials: H
authors.lastname: Stingl
authors.forename: V
authors.initials: V
authors.lastname: Chandramouli
authors.forename: W C
authors.initials: WC
authors.lastname: Schumann
authors.forename: A
authors.initials: A
authors.lastname: Hofer
authors.forename: B R
authors.initials: BR
authors.lastname: Landau
authors.forename: P
authors.initials: P
authors.lastname: Nowotny
authors.forename: W
authors.initials: W
authors.lastname: Waldhäusl
authors.forename: G I
authors.initials: GI
authors.lastname: Shulman
mesh_terms: D000042:Absorption; D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D005943:Gluconeogenesis; D005947:Glucose / Q000096:biosynthesis*; D005990:Glycerol / Q000097:blood / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D009994:Osmolar Concentration; D013004:Somatostatin / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D004338:Drug Combinations; D005217:Fat Emulsions, Intravenous; D005230:Fatty Acids, Nonesterified; D006728:Hormones; D007328:Insulin; D013004:Somatostatin; D006493:Heparin; D005947:Glucose; D005990:Glycerol