Mechanism of regulation of glucose production by lipolysis in humans

1992 ◽  
Vol 262 (3) ◽  
pp. E353-E358 ◽  
Author(s):  
F. Jahoor ◽  
S. Klein ◽  
R. Wolfe
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Nicotinic Acid ◽  
Plasma Insulin ◽  
Glucose Production ◽  
Plasma Free Fatty Acid ◽  
Insulin Levels ◽  
Plasma Insulin Levels ◽  
Normal Humans ◽  
The Relationship

The relationship between the rate of lipolysis and rate of glucose production (Ra) was investigated in 14- and 86-h fasted humans. [6,6-2H]glucose and [2H]5glycerol were infused to measure glucose and glycerol Ra in response to infusions of nicotinic acid in 14- and 86-h fasted subjects (protocol 1). The response of glucose Ra to nicotinic acid alone and nicotinic acid plus unlabeled glycerol was also measured in 86-h fasted subjects (protocol 2). After a 14-h fast, nicotinic acid caused a 30% decrease in plasma insulin levels and a marked (66%) decrease in plasma free fatty acid levels but did not have any significant effect on glucose Ra and concentration. After 86 h of fasting, nicotinic acid decreased glycerol Ra and hence lipolytic rate by approximately 60%. This caused a significant decrease (P less than 0.05) of 16-20% in glucose Ra and uptake. This decrease in glucose Ra was abolished when unlabeled glycerol was also infused with nicotinic acid to maintain glycerol Ra. These findings suggest that, in normal humans, a decrease in the rate of lipolysis regulates glucose Ra via its effect on the availability of glycerol for gluconeogenesis.

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.

Regulation of plasma free fatty acid turnover

1961 ◽  
Vol 201 (1) ◽  
pp. 9-15 ◽  
Author(s):  
D. T. Armstrong ◽  
R. Steele ◽  
N. Altszuler ◽  
A. Dunn ◽  
J. S. Bishop ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Plasma Free Fatty Acid ◽  
Mass Action ◽  
Turnover Rates ◽  
Pharmacological Treatments ◽  
Simple Mass ◽  
Plasma Ffa ◽  
Specific Activities ◽  
The Relationship

Plasma free fatty acid (FFA) turnover rates have been estimated in dogs by a technique involving measurement of FFA specific activities during constant intravenous infusion of trace amounts of C14-labeled palmitic acid. In order to determine the relationship between FFA concentration and turnover, variations in plasma FFA levels ranging from 0.081 to 3.31 µEq/ml were induced by a variety of physiological and pharmacological treatments. Calculated FFA turnover rates ranged from 2.1 to 58.8 µEq/kg/min, with a highly significant linear regression of FFA turnover on FFA level. It is concluded that under a variety of conditions changes in FFA concentration are brought about by changes in FFA production rate and that changes in FFA uptake are simple mass-action effects of changes in FFA concentration. Respiratory C14O2 data are presented indicating that about one-fourth of the total expired CO2 is derived from FFA in the postabsorptive state. This accounts for the immediate fate of about one-fourth of the total FFA leaving the plasma.

Insulin acutely suppresses glucose production by both peripheral and hepatic effects in normal dogs

1998 ◽  
Vol 274 (2) ◽  
pp. E346-E356 ◽  
Author(s):  
Richard H. McCall ◽  
Stephanie R. Wiesenthal ◽  
Z. Qing Shi ◽  
Kenneth Polonsky ◽  
Adria Giacca
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Insulin Infusion ◽  
Low Dose ◽  
Glucose Production ◽  
High Rate ◽  
High Dose ◽  
Insulin Levels ◽  
Predominant Effect

To determine whether the predominant effect of insulin in suppressing tracer-determined glucose production (Ra) is hepatic or peripheral, we infused insulin peripherally (PER) and portally (POR) at both low (0.75 pmol ⋅ kg−1 ⋅ min−1) and high physiological rates (2.7 pmol ⋅ kg−1 ⋅ min−1) during euglycemic clamps in normal dogs. We also infused insulin peripherally at one-half these rates (1/2 PER) to match the peripheral insulin levels in POR and thus obtain a selective POR vs. 1/2 PER difference in hepatic insulin levels. At the high-rate insulin infusion, peripheral insulin levels were greatest with PER (PER = 212 ± 10 pM, n = 5; POR = 119 ± 5 pM, n = 6; 1/2 PER = 122 ± 5 pM, n = 6). Calculated hepatic insulin levels were greatest with POR (POR = 227 ± 13 pM, PER = 206 ± 19 pM, 1/2 PER = 123 ± 8 pM). High-dose PER yielded a greater suppression of Ra than POR (79 ± 18 vs. 56 ± 6%, P < .001). Ra was only suppressed by 45 ± 6% with 1/2 PER ( P< 0.01 vs. POR on 6 paired experiments). Free fatty acid (FFA) was suppressed by 57 ± 8% with PER and only by 33 ± 5 and 37 ± 2% with POR and 1/2 PER, respectively. The low-dose PER and POR yielded an equal Ra suppression (PER = 46 ± 9%, POR = 43 ± 4%). Only 1/2 PER was associated with a lower suppression of Ra (36 ± 8, P < 0.05 vs. POR). FFA showed similar suppression in all three groups (∼25%). Using both insulin infusion rates, the percent Ra suppression per unit difference in peripheral insulin was approximately twofold greater than that per unit difference in hepatic insulin. These results suggest that, during euglycemic clamps without somatostatin in normal dogs, Ra suppression is mediated by both peripheral and hepatic effects of insulin and that peripheral insulin, at least at high physiological infusion rates, is more potent than hepatic insulin in suppressing Ra.

Investigations on the Effect of Nicotinic Acid on Plasma Free Fatty Acid Levels

Pharmacology ◽  
1965 ◽  
Vol 12 (1) ◽  
pp. 8-14
Author(s):  
R. Bombelli ◽  
T. Farkas ◽  
R. Vertua
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Nicotinic Acid ◽  
Plasma Free Fatty Acid

Prevailing hyperglycemia is critical in the regulation of glucose metabolism during exercise in poorly controlled alloxan-diabetic dogs

2005 ◽  
Vol 98 (3) ◽  
pp. 930-939 ◽  
Author(s):  
Michael J. Christopher ◽  
Christian Rantzau ◽  
Glenn McConell ◽  
Bruce E. Kemp ◽  
Frank P. Alford
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Glucose Uptake ◽  
Plasma Glucose ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Plasma Free Fatty Acid ◽  
Glucose Turnover ◽  
Metabolic Clearance ◽  
Hepatic Glucose

The separate impacts of the chronic diabetic state and the prevailing hyperglycemia on plasma substrates and hormones, in vivo glucose turnover, and ex vivo skeletal muscle (SkM) during exercise were examined in the same six dogs before alloxan-induced diabetes (prealloxan) and after 4–5 wk of poorly controlled hyperglycemic diabetes (HGD) in the absence and presence of ∼300-min phlorizin-induced (glycosuria mediated) normoglycemia (NGD). For each treatment state, the ∼15-h-fasted dog underwent a primed continuous 150-min infusion of [3-3H]glucose, followed by a 30-min treadmill exercise test (∼65% maximal oxygen capacity), with SkM biopsies taken from the thigh (vastus lateralis) before and after exercise. In the HGD and NGD states, preexercise hepatic glucose production rose by 130 and 160%, and the metabolic clearance rate of glucose (MCRg) fell by 70 and 37%, respectively, compared with the corresponding prealloxan state, but the rates of glucose uptake into peripheral tissues (Rdtissue) and total glycolysis (GF) were unchanged, despite an increased availability of plasma free fatty acid in the NGD state. Exercise-induced increments in hepatic glucose production, Rdtissue, and plasma-derived GF were severely blunted by ∼30–50% in the NGD state, but increments in MCRg remained markedly reduced by ∼70–75% in both diabetic states. SkM intracellular glucose concentrations were significantly elevated only in the HGD state. Although Rdtissue during exercise in the diabetic states correlated positively with preexercise plasma glucose and insulin and GF and negatively with preexercise plasma free fatty acid, stepwise regression analysis revealed that an individual's preexercise glucose and GF accounted for 88% of Rdtissue during exercise. In conclusion, the prevailing hyperglycemia in poorly controlled diabetes is critical in maintaining a sufficient supply of plasma glucose for SkM glucose uptake during exercise. During phlorizin-induced NGD, increments in both Rdtissue and GF are impaired due to a diminished fuel supply from plasma glucose and a sustained reduction in increments of MCRg.

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