Die Bedeutung freier Fettsäuren für die Regulation der hepatischen Glukoneogenese des Menschen / Dissertant: Harald Stingl

• VerfasserIn: Stingl, Harald Alexander
• Place / Publishing House: [2000]
• Year of Publication: 2000
• Language: German
• Physical Description: VI, 125 Bl.; Ill., graph. Darst.
• Notes: Zsfassung in engl. Sprache

eng: Healthy, lean subjects (n=6) were infused with lipid/heparin (FFA: 2.8 #+- # 0.3 mM; glycerol: 0.5 #+-# 0.1 mM) and glycerol during 9 hours (= control; 0.6 #+-# 0.1 mM; 0.5 #+-# 0.0 mM). During lipid infusion, plasma insulin concentrations rose by #approx#50 % (p;0.05), but neither endogenous glucose production (EGP, estimated with D-[6,6-"2H_2]-glucose) nor fractional gluconeogenesis (GNG, "2H enrichments in C5/C2 of blood glucose following "2H_2O ingestion) were different from control studies. During somatostatin-insulin-glucagon clamp tests at postabsorptive plasma insulin (#approx#35 pM) and glucagon (#approx#90 ng/ml) concentrations, plasma glucose increased by #approx#50 % (p;0.005) during lipid infusion. Rates of EGP remained unchanged (#approx#9.5 #mu#mol*kg"-"1min"-"1). GNG was 62 #+-# 5 % (lipid) and 60 #+-# 6 % (glycerol) at 0 min and dose (p;0.005) to 74 #+-# 3 % during lipid infusion (540 min, p;0.05 vs. glycerol: 64 #+-# 4 %). In a second study, healthy subjects were infused with lipid/heparin (FFA: 2.2 #+-# 0.1 mM; glycerol: 0.5 #+-# 0.03 mM; n=7) , glycerol (0.4 #+-# 0.1 mM; 1.5 #+-# 0.2 mM, n=5) and saline (0.5#+-#0.1 mM; 0.2 #+-# 0.02 mM; n=7). Rates of GNG were calculated by subtracting rates of net glycogen breakdown (decrease of liver glycogen, 9 h, "1"3C NMR spectroscopy) from EGP. EGP decreased by #approx#25 % during lipid and saline, but not during glycerol infusion (p;0.001 vs. lipid, saline). Elevation of plasma FFA or glycerol increased GNG to 96 #+-# 2 % (p;0.001) and 86 #+-# 3 % (p;0.01 vs. saline: 70 #+-# 4 %), respectively. When the lipid-induced rise of portal vein insulin concentrations (p;0.05) was matched employing somatostatin-insulin-glucagon clamps (n=5), GNG (66 #+- # 3 %) did not differ from saline studies. In conclusion, FFA elevation markedly augments GNG without affecting EGP. This effect is neither due to (i) the lipid-induced rise in insulin secretion nor to (ii) increased glycerol availability alone, since very high glycerol concentrations were required for a comparable increase in fractional GNG.