Free Fatty Acids In Man Research Articles

Dose response to insulin in man: differential effects on glucose and ketone body regulation.

This prospective study was undertaken to elucidate the relationship between progressive log increments in plasma free insulin concentration and the resultant changes in the concentrations of plasma glucose, potassium, ketones, and free fatty acids in man. We attempted to define both the maximal and minimal threshold for substrate response relative to circulating concentrations of plasma insulin. Hyperglycemia and hyperketonemia were experimentally induced with dexamethasone in six diabetic subjects. Circulating plasma insulin concentration was acutely elevated by the continuous iv infusion of insulin in order to attain ten-fold increments in circulating plasma insulin concentration. Specifically, following a progressive elevation above basal concentration, maximal increments in circulating plasma insulin of 7 μU/ml, 90μU/ml, and 1, 621 μU/ml were obtained. The differential effects of these acute alterations in plasma insulin concentration on plasma substrate concentrations were compared to a controlsaline...

Determination of splanchnic secretion rate of plasma triglycerides and of total and splanchnic turnover of plasma free fatty acids in man.

Abstract. A method has been developed whereby the splanchnic secretion rate of plasma triglycerides (TG) and the splanchnic uptake and mobilization of plasma free fatty acids (FFA) can be measured in man. The method includes constant intravenous infusion of albumin‐bound 3H‐labelled palmitate, and simultaneous sampling of blood from the hepatic vein and an artery.The methodological problems associated with the quantitative determination of the small hepatio venous‐arterial differences of labelled and unlabelled plasma TG and FFA have been studied. By performing ten estimates on each hepatic vein and arterial sample, analytical precision was increased sufficiently to detect significant hepatic venous‐arterial differences in TG concentration and radioactivity.The splanchnic secretion rates of labelled plasma TG were found to be constant 3 hours after beginning the continous infusion of the precursor 3H‐palmitate. The plasma TG turnover was calculated according to three different methods: the chemical, the isotope and the plasma TG clearance methods. The mean values and standard deviations of the three methods were 59 ± 105, 29 ± 12 and 37 ± 22 μmoles/min.The splanchnic uptake of plasma FFA was estimated to be between 225 and 269 μmoles/min and the splanchnic mobilization of plasma FFA was between 76 and 120 μmoles/min.

Role of acetate in the reduction of plasma free fatty acids produced by ethanol in man

To investigate the mechanism by which ethanol lowers plasma free fatty acids, we tested the ability of two products of alcohol metabolism, acetate and lactate, to lower free fatty acids in man. Sodium acetate was given orally to five healthy fasting volunteers and caused a significant fall in plasma free fatty acids. After amounts of ethanol and acetate that produced similar reductions in free fatty acids, plasma acetate increased 3- to 4-fold within 20 min. In each of three subjects the fall of free fatty acids observed after acetate ingestion occurred at plasma acetate levels less than or equal to those reached after ethanol. In all studies plasma glucose remained stable. Oral administration of sodium lactate to another volunteer in amounts sufficient to raise plasma lactate concentrations to a level similar to that found after ethanol administration failed to lower plasma free fatty acids. Thus acetate, a metabolite of ethanol, reduces plasma free fatty acids at plasma acetate levels comparable to those resulting from ethanol metabolism, which suggests that the lowering of plasma free fatty acids produced by ethanol is mediated, at least in part, by acetate.

The effect of a pyrazole derivative on plasma free fatty acids in man

The level of plasma free fatty acids after an overnight fast is significantly lowered by oral administration of 5-methylpyrazole-3-carboxylic acid. The adipokinetic effects of epinephrine and human growth hormone in normal subjects are markedly reduced by pretreatment with the drug. The compound did not alter blood sugar levels. The pharmacological inhibition of lipolysis offers another means by which the mechanisms of the control of energy metabolism may be investigated.

Investigations on the neurovegetative regulation of the blood level of free fatty acids in man

L'auteur rapporte brievement les resultats de nombreuses experiences propres et de ses collaborateurs visant a modifier chez l'homme le taux sanguin des AGL en influencant le tonus neuro-vegetatif du sujet. Soit les substances sympathomimetiques, soit les vagomimetiques, surtout administrees par voie parenterale, augmentent le taux sanguin des AGL. Pareil effet ont les situations qui s'accompagnent d'une augmentation du tonus sympathique ou d'une stimulation vagale. Les bloquants du vague semblent incapables d'empecher la mobilisation des AGL par l'acetylcholine, tandis que cela peut etre obtenu par les bloquants du sympathique (regitine). La plupart des bloquants du sympathique de type α et sourtout de type β empechent l'augmentation des AGL causee par le «stress», tandis que d'autre part, administres seuls, ils causent une sensible elevation du taux sanguin des AGL.

Serum glucose and free fatty acids in man during prolonged exercise.

Serum glucose and free fatty acids in man during prolonged exercise.

Preparation and properties of growth hormone from equine pituitary glands.

Equine growth hormone has been prepared from acetone-dried residues following extraction of gonadotropins from fresh frozen equine pituitary glands. The growth hormone appeared as a single fraction by gel filtration on Sephadex G-50 and ultracentrifugation. A sedimentation constant of 3.12 was obtained. Preliminary end-group analysis suggested phenylalanine at both aminoand carboxy-terminals. Amino acid analysis of the growth hormone was performed. Four components of equine growth hormone were separated by polyacrylamide column electrophoresis and all 4 were shown to contain growth hormone activity in hypophysectomized rats. Equine growth hormone which contained 0.9 U/mg by assay in hypophysectomized rats neither increased plasma free fatty acids in man nor showed any effect in a balance study in man. It also failed to react immunologically with antisera to human growth hormone, whole and pepsin-digested bovine growth hormone, and bovine albumin. It contained significant prolactin activity but was essenti...

Effect of glucagon on serum insulin, plasma glucose and free fatty acids in man

The response of serum immunoreactive insulin (IRI), plasma glucose and free fatty acids to intravenous glucagon was studied in 9 normal subjects and 2 patients with von Gierke's disease. When comparable levels of arterial hyperglycemia were achieved by paired infusions of glucagon and glucose in normal subjects, glucagon administration was associated with significantly higher concentrations of arterial IRI and, in 4 of the 5 subjects, greater A-V glucose differences. The continuous infusion of glucagon for 3.5 hours in 4 normal subjects was associated with an initial rise and a subsequent decline of IRI and glucose values. FFA levels fell progressively throughout the infusions. The acute administration of glucagon near the termination of these infusions produced significant elevations of IRI with little change in blood glucose or FFA concentrations. Similarly, glucagon administration in 2 patients with von Gierke's disease elevated IRI values without raising the blood glucose. These studies suggest that glucagon can directly stimulate insulin release.

Effect of sympathomimetic compounds with Β-adrenergic effects on plasma free fatty acids in man

Nine sympathomimetic compounds were infused intravenously in man, and their effects on the level of plasma free fatty acids, pulse rate, and blood pressure were recorded. Each compound raised the level of plasma free fatty acids. Its activity in this respect could be correlated with its activity in producing Beta-adrenergic effects on the circulation; both effects were abolished by pretreatment with propranolol. It is concluded that sympathomimetic compounds that stimulate -receptors will raise the plasma concentration of free fatty acids.

Studies on the relation between mobilization of free fatty acids and energy metabolism in man: Effects of norepinephrine and nicotinic acid

The magnitude of the increase in oxygen consumption produced by intravenously infused 1-norepinephrine in fasting young men was well correlated with the increase it produced in plasma level of free fatty acids. The calorigenic effect of norepinephrine was partially inhibited by prior injection of nicotinic acid in quantities sufficient to prevent its fat-mobilizing action. These findings, coupled with the failure of nicotinic acid to affect discernably the effects of norepinephrine on carbohydrate metabolism and cardiovascular and respiratory functions, support the concept that the calorigenic effect of norepinephrine results, in part, from mobilization and oxidation of free fatty acids derived from adipose tissue. Basal energy metabolism was not altered when plasma levels of free fatty acids were reduced by injections of nicotinic acid, but the respiratory quotient rose significantly. These observations suggest that the level of oxidative metabolism is not influenced appreciably in resting adult human subjects by the availability of free fatty acids as fuel and are compatible with the hypothesis that oxidation of carbohydrate is inhibited by utilization of free fatty acids in man.

TURNOVER RATE AND OXIDATION OF DIFFERENT FREE FATTY ACIDS IN MAN DURING EXERCISE.

Palmitate-9, 10-H3 has been infused intravenously at a constant rate together with various C14-labeled fatty acids in healthy subjects at rest and during exercise. No significant differences in the rates of fractional turnover were found between H3-labeled palmitate and C14-labeled palmitate or oleate. Retention of a considerably larger fraction of C14-labeled linoleate in the blood plasma precluded accurate assessment of its fractional turnover rate. The rates of oxidation of palmitate-I-C14, palmitate-U-C14, oleate-I-C14, and linoleate-I-C14 during exercise were similar. The relative abundance of palmitate, oleate, and linoleate in the free fatty acids of plasma changed little during exercise. It is concluded that palmitate-I-C14 is a valid tracer for measuring the turnover rate and oxidation of at least three-fourths of circulating free fatty acids under the conditions of study. Recycling of radioactivity in triglyceride fatty acids of plasma was similar for H3-labeled palmitate and C14-labeled palmitate and oleate, both at rest and during exercise. The plasma concentration of glycerol increased promptly with exercise. Changes in its concentration closely followed those in the turnover rate of free fatty acids, but were of greater magnitude. plasma glycerol during exercise; plasma triglycerides, formation from different FFA; respiratory quotient during exercise Submitted on October 4, 1963

Metabolic effects of two peptides from the anterior pituitary gland.

Two substances, peptides I and II, isolated from a crude extract obtained from the anterior pituitary glands of hogs, had a potent effect on lipid metabolism in rabbits; as little as .02 μg added to leporine adipose tissue in vitro stimulated the release of free fatty acids. Following the injection of 10 μg intravenously, the concentration of free fatty acids in plasma increased threefold within 5 minutes, while 2.5 mg subcutaneously resulted in gross lipemia from 12 to 16 hours later. Their effect in man was slight; from 5 to 25 mg produced only a small increase in free fatty acids in one hour. Similarly, an impure preparation of peptides I and II from human pituitaries failed to produce a clear change in free fatty acids in man. Starch gel electrophoresis of the crude pituitary extract as well as of peptides I and II was performed, and by this method the major component of “Fraction H” prepared by Rudman was identical with peptide II.

Plasma free fatty acid and blood glucose responses to analogues of norepinephrine in man

l -Norepinephrine, l -epinephrine, dl -isoproterenol, and l -α-methyl norepinephrine produced pronounced elevations of plasma free fatty acid (FFA) concentrations in five normal subjects during 30-minute constant infusions at dose rates adjusted to give a pressor response of 45 ± 20 mm Hg. dl -Synephrine produced moderate increases, and tyramine produced minimal increases in FFA levels. Equipressor infusions of dopamine, l -phenylephrine, dl -normetanephrine and l -N-methyl epinephrine produced no significant FFA elevations. The observations suggest that, in derivatives of phenylethylamine, hydroxyl substitution at the para position and on the β-carbon and the presence of a primary or secondary amine structure are associated with the potent ability to elicit elevations of FFA in man. The phenolic hydroxyl group in the meta position appears to be of lesser, though significant, importance. Changes in blood glucose concentration did not always correlate with plasma FFA changes. During infusions of dl -isoproterenol, FFA rose significantly while glucose did not. During infusions of dopamine and l -N-methyl epinephrine, glucose rose significantly while FFA did not.