title: Effects of free fatty acids per se on glucose production, gluconeogenesis, and glycogenolysis.
abstract: Insulin-independent effects of a physiological increase in free fatty acid (FFA) levels on fasting glucose production, gluconeogenesis, and glycogenolysis were assessed by administering [6,6-(2)H(2)]-glucose and deuteriated water ((2)H(2)O) in 12 type 1 diabetic patients, during 6-h infusions of either saline or a lipid emulsion. Insulin was either fully replaced (euglycemic group, n = 6), or underreplaced (hyperglycemic group, n = 6). During saline infusions, plasma FFA levels remained unchanged. Glucose concentrations decreased from 6.7 +/- 0.4 to 5.3 +/- 0.4 mmol/l and 11.9 +/- 1.0 to 10.5 +/- 1.0 mmol/l in the euglycemic and hyperglycemic group, respectively. Accordingly, glucose production declined from 84 +/- 5 to 63 +/- 5 mg x m(-2) x min(-1) and from 84 +/- 5 to 68 +/- 4 mg x m(-2) x min(-1), due to declining rates of glycogenolysis but unaltered rates of gluconeogenesis. During lipid infusions, plasma FFA levels increased twofold. In the euglycemic group, plasma glucose increased from 6.8 +/- 0.3 to 7.8 +/- 0.8 mmol/l. Glucose production declined less in the lipid study than in the saline study due to a stimulation of gluconeogenesis by 6 +/- 1 mg x m(-2) x min(-1) and a decline in glycogenolysis that was 6 +/- 2 mg x m(-2) x min(-1) less in the lipid study than in the saline study. In contrast, in the hyperglycemic group, there were no significant effects of elevated FFA on glucose production, gluconeogenesis, or glycogenolysis. In conclusion, a physiological elevation of plasma FFA levels stimulates glycogenolysis as well as gluconeogenesis and causes mild fasting hyperglycemia. These effects of FFA appear attenuated in the presence of hyperglycemia.
authors.affiliation: Medical Department M, Odense University Hospital, Denmark. pede@dadlnet.dk
authors.forename: Peter
authors.initials: P
authors.lastname: Staehr
authors.forename: Ole
authors.initials: O
authors.lastname: Hother-Nielsen
authors.forename: Bernard R
authors.initials: BR
authors.lastname: Landau
authors.forename: Visvanathan
authors.initials: V
authors.lastname: Chandramouli
authors.forename: Jens Juul
authors.initials: JJ
authors.lastname: Holst
authors.forename: Henning
authors.initials: H
authors.lastname: Beck-Nielsen
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood; D017666:Deuterium Oxide; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005943:Gluconeogenesis / Q000502:physiology*; D015309:Glucose Clamp Technique; D006003:Glycogen / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000097:blood; D007328:Insulin / Q000097:blood* / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D012016:Reference Values
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D006003:Glycogen; D017666:Deuterium Oxide