Fatty acid-independent inhibition of hepatic ketone body production by insulin in humans

1988 ◽  
Vol 254 (6) ◽  
pp. E694-E699 ◽  
Author(s):  
U. Keller ◽  
P. P. Gerber ◽  
W. Stauffacher
Keyword(s):  
Fatty Acid ◽  
Plasma Insulin ◽  
Ketone Body ◽  
Plasma Free Fatty Acid ◽  
Normal Subjects ◽  
Heparin Infusion ◽  
Group A ◽  
Plasma Ffa ◽  
Group B ◽  
Body Production

To investigate whether elevated plasma insulin or glucagon concentrations are capable of modifying hepatic ketogenesis independently of plasma free fatty acid (FFA) concentrations, ketone body production was determined by [3–14C]acetoacetate infusions in overnight-fasted normal subjects during exogenous supply of FFA (Intralipid and heparin infusion). When plasma FFA concentrations were elevated from 0.73 +/- 0.07 to 1.53 +/- 0.16 mmol/l during low insulin concentrations (approximately equal to 13 microU/ml) in group A (n = 7), total ketone body production increased from 3.6 +/- 0.6 to 8.2 +/- 1.0 mumol.kg-1.min-1 (P less than 0.001). When plasma FFA were similarly elevated during raised plasma insulin concentrations (approximately equal to 110 microU/ml) in group B (n = 5), total ketone body production was only 3.8 +/- 0.8 mumol.kg-1.min-1 (P less than 0.01 vs. group A). Low plasma FFA and low insulin concentrations resulted in total ketone body production of 0.70 +/- 0.18 mumol.kg-1.min-1 in group C (n = 7; P less than 0.01 vs. groups A and B). Elevation of plasma glucagon during Intralipid infusion in group D (n = 7) failed to affect ketogenesis, but the beta-hydroxybutyrate-to-acetoacetate concentration ratio decreased significantly (P less than 0.01). The data indicate that elevation of plasma insulin to high physiological concentrations restrains FFA-induced ketogenesis.

Dose-dependent effect of insulin on plasma free fatty acid turnover and oxidation in humans

1990 ◽  
Vol 259 (5) ◽  
pp. E736-E750 ◽  
Author(s):  
R. C. Bonadonna ◽  
L. C. Groop ◽  
K. Zych ◽  
M. Shank ◽  
R. A. DeFronzo
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Lipid Oxidation ◽  
Plasma Insulin ◽  
Plasma Free Fatty Acid ◽  
Whole Body ◽  
Glucose Disposal ◽  
Body Lipid ◽  
Plasma Ffa ◽  
Dose Dependent

Methodology for measuring plasma free fatty acid (FFA) turnover/oxidation with [1–14C]palmitate was tested in normal subjects. In study 1, two different approaches (720-min tracer infusion without prime vs. 150-min infusion with NaH14CO3 prime) to achieve steady-state conditions of 14CO2 yielded equivalent rates of plasma FFA turnover/oxidation. In study 2, during staircase NaH14CO3 infusion, calculated rates of 14CO2 appearance agreed closely with NaH14CO3 infusion rates. In study 3, 300-min euglycemic insulin clamp documented that full biological effect of insulin on plasma FFA turnover/oxidation was established within 60–120 min. In study 4, plasma insulin concentration was raised to 14 +/- 2, 23 +/- 2, 38 +/- 2, 72 +/- 5, and 215 +/- 10 microU/ml. A dose-dependent insulin suppression of plasma FFA turnover/oxidation was observed. Plasma FFA concentration correlated positively with plasma FFA turnover/oxidation in basal and insulinized states. Total lipid oxidation (indirect calorimetry) was significantly higher than plasma FFA oxidation in the basal state, suggesting that intracellular lipid stores contributed to whole body lipid oxidation. Hepatic glucose production and total glucose disposal showed the expected dose-dependent suppression and stimulation, respectively, by insulin. In conclusion, insulin regulation of plasma FFA turnover/oxidation is maximally manifest at low physiological plasma insulin concentrations, and in the basal state a significant contribution to whole body lipid oxidation originates from lipid pool(s) that are different from plasma FFA.

Stimulatory effect of norepinephrine on ketogenesis in normal and insulin-deficient humans

1984 ◽  
Vol 247 (6) ◽  
pp. E732-E739 ◽  
Author(s):  
U. Keller ◽  
P. P. Gerber ◽  
W. Stauffacher
Keyword(s):  
Ketone Body ◽  
Ketone Bodies ◽  
Plasma Free Fatty Acid ◽  
Normal Subjects ◽  
Plasma Norepinephrine ◽  
Metabolic Clearance ◽  
Insulin Deficiency ◽  
Norepinephrine Infusion ◽  
Normal Humans ◽  
Body Production

Elevation of plasma norepinephrine concentrations to stress levels (1,800 pg/ml) resulted in normal subjects in a significant increase in ketone body production by 155% (determined by use of [14C]acetoacetate infusions), in a decrease of the metabolic clearance rate by 38%, hyperketonemia, and in increased plasma free fatty acid (FFA) levels by 57% after 75 min. Norepinephrine infusion during somatostatin-induced insulin deficiency resulted in an augmented and sustained increase in ketone body concentrations due to increased production and decreased peripheral clearance of ketone bodies. Norepinephrine's stimulatory effect on lipolysis waned with time, and its effect on ketogenesis in normal subjects was greater than its influence on plasma FFA levels, and thus presumably on hepatic FFA uptake, suggesting a direct stimulatory effect on hepatic ketogenesis. The data demonstrate that in normal humans the hyperketonemic effect of elevated plasma norepinephrine concentrations results from a combination of three factors: increased ketone body production from augmented FFA supply to the liver; accelerated hepatic ketogenesis; and modestly decreased metabolic clearance of ketone bodies. Acute insulin deficiency augments all these effects and results in progressive ketosis.

Influence of hypothyroidism on the lipolytic activity of norepinephrine in the newborn lamb

1986 ◽  
Vol 108 (3) ◽  
pp. 451-454 ◽  
Author(s):  
C. Wrutniak ◽  
G. Cabello
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Thyroid Hormones ◽  
Lipolytic Activity ◽  
Plasma Free Fatty Acid ◽  
Newborn Lamb ◽  
Group A ◽  
Group B ◽  
Infusion Of Norepinephrine ◽  
Medium Group

ABSTRACT The effects of hypothyroidism on the lipolytic activity of norepinephrine were assessed in the newborn lamb. Lambs were separated into three groups: group A were controls; groups B and C were made hypothyroid by administration of benzylthiouracil from birth until 11 days of age. In control lambs, plasma free fatty acid concentrations, used as an index of lipolytic activity, increased significantly (plus 0·45 mmol/l) during the infusion of norepinephrine, whereas they did not change in hypothyroid lambs (group B). Adding thyroxine and tri-iodothyronine to the infusion medium (group C) immediately restored the free fatty acid response to norepinephrine in hypothyroid lambs (plus 0·41 mmol/l). These results suggest that thyroid hormones could modulate the lipolytic activity of catecholamines in the newborn lamb without a latent period. J. Endocr. (1986) 108, 451–454

Relationship between fatty acid delivery and fatty acid oxidation during strenuous exercise

1995 ◽  
Vol 79 (6) ◽  
pp. 1939-1945 ◽  
Author(s):  
J. A. Romijn ◽  
E. F. Coyle ◽  
L. S. Sidossis ◽  
X. J. Zhang ◽  
R. R. Wolfe
Keyword(s):  
Fatty Acid ◽  
Plasma Free Fatty Acid ◽  
Fat Oxidation ◽  
Carbohydrate Oxidation ◽  
Strenuous Exercise ◽  
Constant Infusion ◽  
Acid Oxidation ◽  
Heparin Infusion ◽  
Plasma Ffa ◽  
Total Fat

To evaluate the extent to which decreased plasma free fatty acid (FFA) concentration contributes to the relatively low rates of fat oxidation during high-intensity exercise, we studied FFA metabolism in six endurance-trained cyclists during 20–30 min of exercise [85% of maximal O2 uptake (VO2max)]. They were studied on two occasions: once during a control trial when plasma FFA concentration is normally low and again when plasma FFA concentration was maintained between 1 and 2 mM by intravenous infusion of lipid (Intralipid) and heparin. During the 20–30 min of exercise, fat and carbohydrate oxidation were measured by indirect calorimetry, and the rates of appearance (Ra) of plasma FFA and glucose were determined by the constant infusion of [6,6–2H2]glucose and [2H2]palmitate. Lipid-heparin infusion did not influence the Ra or rate of disappearance of glucose. During exercise in the control trial, Ra FFA failed to increase above resting levels (11.0 +/- 1.2 and 12.4 +/- 1.7 mumol.kg-1.min-1 for rest and exercise, respectively) and plasma FFA concentration dropped from a resting value of 0.53 +/- 0.08 to 0.29 +/- 0.02 mM. The restoration of plasma FFA concentration resulted in a 27% increase in total fat oxidation (26.7 +/- 2.6 vs. 34.0 +/- 4.4 mumol.kg-1.min-1, P < 0.05) with a concomitant reduction in carbohydrate oxidation, apparently due to a 15% (P < 0.05) reduction in muscle glycogen utilization. However, the elevation of plasma FFA concentration during exercise at 85% VO2max only partially restored fat oxidation compared with the levels observed during exercise at 65% VO2max. These findings indicate that fat oxidation is normally impaired during exercise at 85% VO2max because of the failure of FFA mobilization to increase above resting levels, but this explains only part of the decline in fat oxidation when exercise intensity is increased from 65 to 85% VO2max.

Increased insulin suppression of plasma free fatty acid concentration in exercise-trained rats

1993 ◽  
Vol 74 (1) ◽  
pp. 293-296 ◽  
Author(s):  
J. M. Lavoie ◽  
J. Bongbele ◽  
S. Cardin ◽  
M. Belisle ◽  
J. Terrettaz ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Exercise Training ◽  
Plasma Insulin ◽  
Plasma Free Fatty Acid ◽  
Mean Value ◽  
Free Fatty Acid Concentration ◽  
Mean Diameter ◽  
Plasma Ffa ◽  
Fat Depot

The effect of exercise training on the insulin suppression of plasma free fatty acid (FFA) concentrations was studied in unanesthetized rats with the hyperinsulinemic-euglycemic clamp technique. Seven rats trained (TR) for 3 h/day by continuous swimming during 8 wk were compared with 6 untrained (UT) body weight-matched rats. Both TR and UT rats were submitted to an exercise swimming session 18 h before the clamp. A smaller mean diameter of adipocytes sampled from the epididymal fat depot was measured in TR animals. The total quantity of glucose infused to maintain euglycemia was 2.2 times higher in TR than in UT animals. No significant differences in plasma insulin concentrations were found between the two groups throughout the experiment. Insulin infusions resulted in a 60% decrease of plasma FFA in TR rats (mean value: from 0.46 to 0.18 mM) compared with 27% in UT animals (mean value: from 0.45 to 0.33 mM). The data indicate a greater ability of insulin to suppress plasma FFA levels with exercise training, which suggests an increased antilipolytic action of insulin in adipocytes under this condition.

The Effects of Cold and Prostaglandin E1 on Lipid Mobilization in the Chicken

1971 ◽  
Vol 49 (5) ◽  
pp. 394-398 ◽  
Author(s):  
W. D. Wagner ◽  
R. A. Peterson ◽  
R. J. Cenedella
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Cold Exposure ◽  
Prostaglandin E1 ◽  
Plasma Free Fatty Acid ◽  
Prostaglandin E ◽  
Elevated Plasma ◽  
Lower Plasma ◽  
Lipid Mobilization ◽  
Plasma Ffa

Plasma free fatty acid (FFA) levels and the effects of prostaglandin E1 (PGE1) were studied in cold-acclimated and cold-exposed chickens and compared to controls. Chickens cold-acclimated at 4–7 or 8–11 °C for 4 weeks had significantly elevated plasma FFA when compared to the controls at 19–21 °C. Although PGE1 had no effect on the basal level of FFA of controls, a significantly lower plasma FFA was seen after injection of either 10 or 30 μg PGE1/kg in cold-acclimated chickens. Chickens cold-exposed to 2–3 °C for 4 h demonstrated significant elevations of plasma FFA when compared to controls. Only 30 μg PGE1/kg significantly depressed the plasma FFA in the cold-exposed birds. No inhibition of basal FFA release was seen in control animals. From these experiments, it is concluded that chickens mobilize FFA extensively under cold-exposure and that this stimulated lipolysis is inhibited by PGE1.

Reduced plasma FFA availability increases net triacylglycerol degradation, but not GPAT or HSL activity, in human skeletal muscle

2004 ◽  
Vol 287 (1) ◽  
pp. E120-E127 ◽  
Author(s):  
Matthew J. Watt ◽  
Anna G. Holmes ◽  
Gregory R. Steinberg ◽  
Jose L. Mesa ◽  
Bruce E. Kemp ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Body Fat ◽  
Plasma Free Fatty Acid ◽  
Fat Oxidation ◽  
Dry Mass ◽  
Hormone Sensitive Lipase ◽  
Whole Body ◽  
Plasma Ffa

Intramuscular triacylglycerols (IMTG) are proposed to be an important metabolic substrate for contracting muscle, although this remains controversial. To test the hypothesis that reduced plasma free fatty acid (FFA) availability would increase IMTG degradation during exercise, seven active men cycled for 180 min at 60% peak pulmonary O2 uptake either without (CON) or with (NA) prior ingestion of nicotinic acid to suppress adipose tissue lipolysis. Skeletal muscle and adipose tissue biopsy samples were obtained before and at 90 and 180 min of exercise. NA ingestion decreased ( P < 0.05) plasma FFA at rest and completely suppressed the exercise-induced increase in plasma FFA (180 min: CON, 1.42 ± 0.07; NA, 0.10 ± 0.01 mM). The decreased plasma FFA during NA was associated with decreased ( P < 0.05) adipose tissue hormone-sensitive lipase (HSL) activity (CON: 13.9 ± 2.5, NA: 9.1 ± 3.0 nmol·min−1·mg protein−1). NA ingestion resulted in decreased whole body fat oxidation and increased carbohydrate oxidation. Despite the decreased whole body fat oxidation, net IMTG degradation was greater in NA compared with CON (net change: CON, 2.3 ± 0.8; NA, 6.3 ± 1.2 mmol/kg dry mass). The increased IMTG degradation did not appear to be due to reduced fatty acid esterification, because glycerol 3-phosphate activity was not different between trials and was unaffected by exercise (rest: 0.21 ± 0.07; 180 min: 0.17 ± 0.04 nmol·min−1·mg protein−1). HSL activity was not increased from resting rates during exercise in either trial despite elevated plasma epinephrine, decreased plasma insulin, and increased ERK1/2 phosphorylation. AMP-activated protein kinase (AMPK)α1 activity was not affected by exercise or NA, whereas AMPKα2 activity was increased ( P < 0.05) from rest during exercise in NA and was greater ( P < 0.05) than in CON at 180 min. These data suggest that plasma FFA availability is an important mediator of net IMTG degradation, and in the absence of plasma FFA, IMTG degradation cannot maintain total fat oxidation. These changes in IMTG degradation appear to disassociate, however, from the activity of the key enzymes responsible for synthesis and degradation of this substrate.

Training-induced elevation in FABPPM is associated with increased palmitate use in contracting muscle

1999 ◽  
Vol 87 (1) ◽  
pp. 285-293 ◽  
Author(s):  
Lorraine P. Turcotte ◽  
Jason R. Swenberger ◽  
Michelle Z. Tucker ◽  
Alice J. Yee
Keyword(s):  
Fatty Acid ◽  
Endurance Training ◽  
Plasma Membranes ◽  
Plasma Free Fatty Acid ◽  
Fatty Acid Binding Proteins ◽  
Fatty Acid Binding ◽  
Palmitate Oxidation ◽  
Plasma Ffa ◽  
Ffa Metabolism ◽  
Red And White Muscles

To evaluate the effects of endurance training in rats on fatty acid metabolism, we measured the uptake and oxidation of palmitate in isolated rat hindquarters as well as the content of fatty acid-binding proteins in the plasma membranes (FABPPM) of red and white muscles from 16 trained (T) and 18 untrained (UT) rats. Hindquarters were perfused with 6 mM glucose, 1,800 μM palmitate, and [1-14C]palmitate at rest and during electrical stimulation (ES) for 25 min. FABPPM content was 43–226% higher in red than in white muscles and was increased by 55% in red muscles after training. A positive correlation was found to exist between succinate dehydrogenase activity and FABPPM content in muscle. Palmitate uptake increased by 64–73% from rest to ES in both T and UT and was 48–57% higher in T than UT both at rest (39.8 ± 3.5 vs. 26.9 ± 4.4 nmol ⋅ min−1 ⋅ g−1, T and UT, respectively) and during ES (69.0 ± 6.1 vs. 43.9 ± 4.4 nmol ⋅ min−1 ⋅ g−1, T and UT, respectively). While the rats were resting, palmitate oxidation was not affected by training; palmitate oxidation during ES was higher in T than UT rats (14.8 ± 1.3 vs. 9.3 ± 1.9 nmol ⋅ min−1 ⋅ g−1, T and UT, respectively). In conclusion, endurance training increases 1) plasma free fatty acid (FFA) uptake in resting and contracting perfused muscle, 2) plasma FFA oxidation in contracting perfused muscle, and 3) FABPPM content in red muscles. These results suggest that an increased number of these putative plasma membrane fatty acid transporters may be available in the trained muscle and may be implicated in the regulation of plasma FFA metabolism in skeletal muscle.

Urinary excretion of glycated protein determined with a specific radioimmunoassay

1991 ◽  
Vol 37 (4) ◽  
pp. 504-507 ◽  
Author(s):  
Chizuko Ukita ◽  
Mitsushige Nishikawa ◽  
Akira Shouzu ◽  
Mitsuo Inada
Keyword(s):  
Urinary Excretion ◽  
Normal Subjects ◽  
Mean Values ◽  
Specific Radioimmunoassay ◽  
Glycated Protein ◽  
Highly Sensitive ◽  
Significant Difference ◽  
Group A ◽  
The Mean ◽  
Group B

Abstract We developed a simple and highly sensitive RIA for glycated protein (GP), and used it to measure GP in serum and urine from 15 normal controls and 30 diabetics (14 with urinary excretion rate of albumin, Ualb less than 15 micrograms/min, group A; nine with 15 less than or equal to Ualb less than or equal to 150 micrograms/min, group B; and seven with Ualb greater than 150 micrograms/min, group C). The mean serum concentration of GP was above normal in all groups of diabetics, and the mean glycation ratios of serum protein (SGP) were higher in groups B and C than in normal subjects. Urinary concentrations of GP also were increased in groups B and C, although the glycation ratio of urinary protein (UGP) was decreased in group C. Consequently, the selectivity of urinary excretion of GP (UGP/SGP) was significantly decreased in group C. Moreover, there was a significant difference in the mean values of selectivity between groups of patients with various degrees of retinopathy. We suggest that measurements of serum and urinary GP are useful to evaluate the progression of diabetic complications.

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