TY - JOUR
T1 - Effects of free fatty acids per se on glucose production, gluconeogenesis, and glycogenolysis.
AU - Staehr, Peter
AU - Hother-Nielsen, Ole
AU - Landau, Bernard R
AU - Chandramouli, Visvanathan
AU - Holst, Jens Juul
AU - Beck-Nielsen, Henning
N1 - Keywords: Adult; Blood Glucose; C-Peptide; Deuterium Oxide; Diabetes Mellitus, Type 1; Fatty Acids, Nonesterified; Gluconeogenesis; Glucose Clamp Technique; Glycogen; Humans; Hyperglycemia; Insulin; Kinetics; Male; Reference Values
PY - 2003
Y1 - 2003
N2 - 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.
AB - 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.
M3 - Journal article
C2 - 12540595
SN - 0012-1797
VL - 52
SP - 260
EP - 267
JO - Diabetes
JF - Diabetes
IS - 2
ER -
