6-6-dideuteroglucose and Hyperinsulinism

Elevation of plasma concentrations of nonesterified fatty acids (NEFA) has been reported to result in protein sparing and in impaired insulin-mediated glucose metabolism. To assess the influence of the chain length of fatty acids on these effects, medium-chain (MC) and long-chain (LC) fatty acid-containing lipid emulsions (2 mg/kg/min each) combined with heparin were administered during 390 minutes to 25 healthy overnight-fasted male subjects. Whole body leucine flux (a parameter of whole body protein breakdown) decreased during MC triglycerides (MCT) by 20% (P <.005). Irreversible leucine catabolism (oxidation of [1-(13)C]-leucine) decreased during LC triglycerides (LCT) by 40% (P <.01) but not during MCT when compared to controls receiving glycerol infusions. MCT administration resulted in a marked (52 %, P <.001) decrease of alpha-ketoisocaproate (alpha-KIC) concentration, suggesting diminished leucine transamination and decreased leucine nonoxidative disappearance (P <.015). Hyperinsulinemia (30 to 40 microU/mL, euglycemic clamping) resulted in decreased leucine flux and oxidation during both lipid infusions, particularly during MCT. The increase in glucose disappearance during hyperinsulinemia in subjects receiving MCT or LCT was less than in controls, and endogenous glucose production measured by 6,6-D(2)-glucose infusions was less suppressed (P <.01). Thus, elevation of plasma LC fatty acids (but not of MC fatty acids) results in decreased leucine oxidation (protein catabolism). This protein-sparing effect of LCT appears to be dissociated from fatty acid effects on glucose metabolism; both MCT and LCT diminished insulin's ability to increase glucose disappearance and to decrease hepatic glucose production.

Topics: Adult; C-Peptide; Carbon Isotopes; Fatty Acids; Fatty Acids, Nonesterified; Glucagon; Glucose; Glucose Clamp Technique; Humans; Hyperinsulinism; Infusions, Intravenous; Insulin; Keto Acids; Lactic Acid; Leucine; Liver; Male; Oxidation-Reduction; Proteins; Reference Values; Triglycerides

The liver is inaccessible to organ balance measurements in humans. To validate [(18)F]fluorodeoxyglucose ([(18)F]FDG) positron emission tomography (PET) in the quantification of hepatic glucose uptake (HGU), we determined [(18)F]FDG modeling parameters, lumped constant (LC), and input functions (single arterial versus dual).. Anesthetized pigs were studied during fasting (n = 6), physiologic (n = 4), and supraphysiologic (n = 4) hyperinsulinemia. PET was performed with C(15)O (blood pool) and [(18)F]FDG (glucose uptake). 6,6-Deuterated glucose ([(2)H]G) was coinjected with [(18)F]FDG and blood collected from the carotid artery and portal and hepatic veins to compute LC as ratio between tracers fractional extraction. HGU was estimated from PET images and ex vivo from high-performance liquid chromatography measurements of liver [(18)F]FDG versus [(18)F]FDG-6-phosphate and [(18)F]-glycogen. Endogenous glucose production was measured with [(2)H]G and hepatic blood flow by flowmeters.. HGU was increased in hyperinsulinemia versus fasting (P < .05). Fractional extraction of [(18)F]FDG and [(2)H]G was similar (not significant), intercorrelated (r = 0.98, P < .0001), and equally higher during hyperinsulinemia than fasting (P 0.95, P < .0001), with a modest underestimation of HGU by the former.. [(18)F]FDG-PET-derived parameters provide accurate quantification of HGU and estimates of liver perfusion and glucose production. In the liver, LC of [(18)F]FDG is nearly unitary. Using a single arterial input introduces only a small error in estimation of HGU.

Topics: Animals; Blood Flow Velocity; Blood Glucose; Chromatography, High Pressure Liquid; Fasting; Fluorodeoxyglucose F18; Glucose; Glucose-6-Phosphate; Glycogen; Hepatic Artery; Hyperinsulinism; Insulin; Liver; Liver Circulation; Models, Biological; Portal Vein; Positron-Emission Tomography; Radiopharmaceuticals; Swine