Acipimox increases glucose disposal in normal man independent of changes in plasma nonesterified fatty acid concentration and whole-body lipid oxidation rate

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.

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Effect of glycemia and nonesterified fatty acids on forearm glucose uptake in normal humans

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1991.261.3.e304 ◽

1991 ◽

Vol 261 (3) ◽

pp. E304-E311 ◽

Cited By ~ 1

Author(s):

M. Walker ◽

G. R. Fulcher ◽

C. F. Sum ◽

H. Orskov ◽

K. G. Alberti

Keyword(s):

Fatty Acid ◽

Blood Glucose ◽

Glucose Uptake ◽

Whole Body ◽

Glucose Disposal ◽

Nonesterified Fatty Acid ◽

Nonesterified Fatty Acids ◽

Glucose Levels ◽

And Control ◽

Blood Glucose Concentrations

The purpose of this study was to examine the effect of physiological plasma nonesterified fatty acid (NEFA) levels on insulin-stimulated forearm and whole body glucose uptake and substrate oxidation during euglycemia and hyperglycemia. Seven healthy men received Intralipid and heparin for 210 min in two studies, with saline as control in two further studies. Insulin (0.05 U.kg-1.h-1) was infused from 60 min, and euglycemia was maintained during lipid (EL) and control (EC) studies, and hyperglycemia was maintained in the other studies (HL and HC). Forearm NEFA uptake was comparable in the lipid studies (+61 +/- 10 and +52 +/- 8 nmol.100 ml forearm-1.min-1, EL and HL) and was suppressed in the controls. With Intralipid, forearm glucose uptake decreased during euglycemia but not during hyperglycemia (+3.85 +/- 0.34 vs. +3.34 +/- 0.25 mumol.100 ml forearm-1.min-1, EC vs. EL, P less than 0.02), with comparable changes in whole body glucose uptake. Glucose oxidation and forearm alanine release decreased with Intralipid at both blood glucose levels, with no significant change in the rates of nonoxidative glucose disposal. These observations support the operation of the glucose-fatty acid cycle at physiological plasma NEFA levels at both blood glucose concentrations, but this was associated with a decrease in peripheral insulin sensitivity only during euglycemia.

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Crude glycerin decreases nonesterified fatty acid concentration in ewes during late gestation and early lactation1

Journal of Animal Science ◽

10.2527/jas.2016.0999 ◽

2017 ◽

Vol 95 (2) ◽

pp. 875-883

Author(s):

D. M. Polizel ◽

I. Susin ◽

R. S. Gentil ◽

E. M. Ferreira ◽

R. A. de Souza ◽

...

Keyword(s):

Fatty Acid ◽

Acid Concentration ◽

Late Gestation ◽

Crude Glycerin ◽

Fatty Acid Concentration ◽

Nonesterified Fatty Acid

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Effect of increased free fatty acid supply on glucose metabolism and skeletal muscle glycogen synthase activity in normal man

Clinical Science ◽

10.1042/cs0820219 ◽

1992 ◽

Vol 82 (2) ◽

pp. 219-226 ◽

Cited By ~ 51

Author(s):

A. B. Johnson ◽

M. Argyraki ◽

J. C. Thow ◽

B. G. Cooper ◽

G. Fulcher ◽

...

Keyword(s):

Skeletal Muscle ◽

Fatty Acid ◽

Lipid Oxidation ◽

Muscle Glycogen ◽

Glucose Oxidation ◽

Glycogen Synthase ◽

Whole Body ◽

Glucose Disposal ◽

Oxidation Rates ◽

Glycogen Synthase Activity

1. Experimental elevation of plasma non-esterified fatty acid concentrations has been postulated to decrease insulin-stimulated glucose oxidation and storage rates. Possible mechanisms were examined by measuring skeletal muscle glycogen synthase activity and muscle glycogen content before and during hyperinsulinaemia while fasting plasma non-esterified fatty acid levels were maintained. 2. Fasting plasma non-esterified fatty acid levels were maintained in seven healthy male subjects by infusion of 20% (w/v) Intralipid (1 ml/min) for 120 min before and during a 240 min hyperinsulinaemic euglycaemic clamp (100 m-units h−1 kg−1) combined with indirect calorimetry. On the control day, 0.154 mol/l NaCl was infused. Vastus lateralis muscle biopsy was performed before and at the end of the insulin infusion. 3. On the Intralipid study day serum triacylglycerol (2.24 ± 0.20 versus 0.67 ± 0.10 mmol/l), plasma non-esterified fatty acid (395 ± 13 versus 51 ± 1 μmol/l), blood glycerol (152 ± 2 versus 11 ± 1 μmol/l) and blood 3-hydroxybutyrate clamp levels [mean (95% confidence interval)] [81 (64–104) versus 4 (3–5) μmol/l] were all significantly higher (all P < 0.001) than on the control study day. Lipid oxidation rates were also elevated (1.07 ± 0.07 versus 0.27 ± 0.08 mg min−1 kg−1, P < 0.001). During the clamp with Intralipid infusion, insulin-stimulated whole-body glucose disposal decreased by 28% (from 8.53 ± 0.77 to 6.17 ± 0.71 mg min−1 kg−1, P < 0.005). This was the result of a 48% decrease in glucose oxidation (3.77 ± 0.32 to 1.95 ± 0.21 mg min−1 kg−1, P<0.001), with no significant change in nonoxidative glucose disposal (4.76 ± 0.49 to 4.22 ± 0.57 mg min−1 kg−1, not significant). 4. Basal and insulin-stimulated glycogen synthase activities (13.1 ± 1.9 versus 11.4 ± 2.3% and 30.8 ± 2.3 versus 27.6 ± 4.5%, respectively) were unaffected by the increased plasma non-esterified fatty acid levels. Similarly, basal (36.1 ± 2.7 versus 37.2 ± 1.4 μmol/g) and stimulated (40.0 ± 0.6 versus 37.6 ± 4.4 μmol/g) muscle glycogen levels were unaltered. Insulin-stimulated hexokinase activity was also not affected (0.52 ± 0.08 versus 0.60 ± 0.08 units/g wet weight). 5. Maintenance of plasma non-esterified fatty acid levels at fasting values resulted in an increase in lipid oxidation and was associated with a decrease in insulin-stimulated whole-body glucose uptake and glucose oxidation rates, but no change in non-oxidative glucose disposal. Increased plasma non-esterified fatty acid levels did not appear to have a direct inhibitory effect on glycogen synthase activity or storage of glucose as glycogen at these insulin levels.

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