scholarly journals Glucose metabolism in isolated brown adipocytes under β-adrenergic stimulation. Quantitative contribution of glucose to total thermogenesis

1987 ◽  
Vol 245 (3) ◽  
pp. 789-793 ◽  
Author(s):  
D Isler ◽  
H P Hill ◽  
M K Meier
Keyword(s):  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Glucose Oxidation ◽  
Lactate Production ◽  
O2 Consumption ◽  
Adrenergic Stimulation ◽  
Brown Adipocytes ◽  
Beta Agonists ◽  
Brown Adipose ◽  
Total Glucose

To quantify the potential of brown adipose tissue as a target organ for glucose oxidation, O2 consumption and glucose metabolism in isolated rat brown adipocytes were measured in the presence and absence of insulin, by using the beta-agonists isoprenaline or Ro 16-8714 to stimulate thermogenesis. Basal metabolic rate (278 mumol of O2/h per g of lipid) was maximally stimulated with isoprenaline (20 nm) and Ro 16-8714 (20 microM) to 1633 and 1024 mumol of O2/h per g respectively, whereas insulin had no effect on O2 consumption. Total glucose uptake, derived from the sum of [U-14C]glucose incorporation into CO2 and total lipids and lactate release, was enhanced with insulin. Isoprenaline and Ro 16-8714 had no effect on insulin-induced glucose uptake, but promoted glucose oxidation while inhibiting insulin-dependent lipogenesis and lactate production. A maximal value for glucose oxidation was obtained under the combined action of Ro 16-8714 and insulin, which corresponded to an equivalent of 165 mumol of O2/h per g of lipid. This makes it clear that glucose is a minor substrate for isolated brown adipocytes, fuelling thermogenesis by a maximum of 16%.

scholarly journals Interscapular brown adipose tissue denervation does not promote the oxidative activity of inguinal white adipose tissue in male mice

2018 ◽  
Vol 315 (5) ◽  
pp. E815-E824 ◽  
Author(s):  
Sébastien M. Labbé ◽  
Alexandre Caron ◽  
William T. Festuccia ◽  
Roger Lecomte ◽  
Denis Richard
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Glucose Uptake ◽  
White Adipose Tissue ◽  
Oxidative Activity ◽  
Substrate Uptake ◽  
Adrenergic Stimulation ◽  
Brown Adipocytes ◽  
Apparent Lack ◽  
Brown Adipose

Brown adipose tissue (BAT) thermogenesis is a key controller of energy metabolism. In response to cold or other adrenergic stimuli, brown adipocytes increase their substrate uptake and oxidative activity while uncoupling ATP synthesis from the mitochondrial respiratory chain activity. Brown adipocytes are found in classic depots such as in the interscapular BAT (iBAT). They can also develop in white adipose tissue (WAT), such as in the inguinal WAT (iWAT), where their presence has been associated with metabolic improvements. We previously reported that the induction of oxidative metabolism in iWAT is low compared with that of iBAT, even after sustained adrenergic stimulation. One explanation to this apparent lack of thermogenic ability of iWAT is the presence of an active iBAT, which may prevent the full activation of iWAT. In this study, we evaluated whether iBAT denervation-induced browning of white fat enhanced the thermogenic activity of iWAT following cold acclimation, under beta-3 adrenergic stimulation (CL 316,243). Following a bilateral denervation of iBAT, we assessed energy balance, evaluated the oxidative activity of iBAT and iWAT using 11C-acetate, and quantified the dynamic glucose uptake of those tissues using 2-deoxy-2-[18F]- fluoro-d-glucose. Our results indicate that despite portraying marked browning and mildly enhanced glucose uptake, iWAT of cold-adapted mice does not exhibit significant oxidative activity following beta-3 adrenergic stimulation in the absence of a functional iBAT. The present results suggest that iWAT is not readily recruitable as a thermogenic organ even when functional iBAT is lacking.

scholarly journals β3-Adrenergic Stimulation Differentially Inhibits Insulin Signaling and Decreases Insulin-induced Glucose Uptake in Brown Adipocytes

1999 ◽  
Vol 274 (49) ◽  
pp. 34795-34802 ◽  
Author(s):  
Johannes Klein ◽  
Mathias Fasshauer ◽  
Moriko Ito ◽  
Bradford B. Lowell ◽  
Manuel Benito ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Insulin Signaling ◽  
Adrenergic Stimulation ◽  
Brown Adipocytes

scholarly journals Noradrenaline increases glucose transport into brown adipocytes in culture by a mechanism different from that of insulin

1996 ◽  
Vol 314 (2) ◽  
pp. 485-490 ◽  
Author(s):  
Yasutake SHIMIZU ◽  
Danuta KIELAR ◽  
Yasuhiko MINOKOSHI ◽  
Takashi SHIMAZU
Keyword(s):  
Cyclic Amp ◽  
Glucose Uptake ◽  
Glucose Transport ◽  
Glucose Transporter ◽  
Sympathetic Nerves ◽  
Intrinsic Activity ◽  
Brown Adipocytes ◽  
Brown Adipose ◽  
Km Value ◽  
Glucose Transporter Glut4

Glucose uptake into brown adipose tissue has been shown to be enhanced directly by noradrenaline (norepinephrine) released from sympathetic nerves. In this study we characterized the glucose transport system in cultured brown adipocytes, which responds to noradrenaline as well as insulin, and analysed the mechanism underlying the noradrenaline-induced increase in glucose transport. Insulin increased 2-deoxyglucose (dGlc) uptake progressively at concentrations from 10-11 to 10-6 M, with maximal stimulation at 10-7 M. Noradrenaline concentrations ranging from 10-8 to 10-6 M also enhanced dGlc uptake, even in the absence of insulin. The effects of noradrenaline and insulin on dGlc uptake were additive. The stimulatory effect of noradrenaline was mimicked by the β3-adrenergic agonist, BRL37344, at concentrations two orders lower than noradrenaline. Dibutyryl cyclic AMP also mimicked the stimulatory effect of noradrenaline, and the antagonist of cyclic AMP, cyclic AMP-S Rp-isomer, blocked the enhancement of glucose uptake due to noradrenaline. Furthermore Western blot analysis with an anti-phosphotyrosine antibody revealed that, in contrast with insulin, noradrenaline apparently does not stimulate intracellular phosphorylation of tyrosine, suggesting that the noradrenaline-induced increase in dGlc uptake depends on elevation of the intracellular cyclic AMP level and not on the signal chain common to insulin. When cells were incubated with insulin, the content of the muscle/adipocyte type of glucose transporter (GLUT4) in the plasma membrane increased, with a corresponding decrease in the amount in the microsomal membrane. In contrast, noradrenaline did not affect the subcellular distribution of GLUT4 or that of the HepG2/erythrocyte type of glucose transporter. Although insulin increased Vmax. and decreased the Km value for glucose uptake, the effect of noradrenaline was restricted to a pronounced decrease in Km. These results suggest that the mechanism by which noradrenaline stimulates glucose transport into brown adipocytes is not due to translocation of GLUT but is probably due to an increase in the intrinsic activity of GLUT, which is mediated by a cyclic AMP-dependent pathway.

Basal plasma insulin levels exert a qualitative but not quantitative effect on glucose-mediated glucose uptake

1995 ◽  
Vol 268 (6) ◽  
pp. E1089-E1095 ◽  
Author(s):  
S. Del Prato ◽  
A. Riccio ◽  
S. Vigili de Kreutzenberg ◽  
M. Dorella ◽  
A. Tiengo ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Glucose Oxidation ◽  
Critical Role ◽  
Glucose Disposal ◽  
Insulin Levels ◽  
Hyperglycemic Clamp ◽  
Basal Plasma ◽  
Plasma Insulin Levels ◽  
Total Body

We assessed the effect of hyperglycemia on glucose uptake in the presence of normal basal insulin levels or somatostatin-induced hypoinsulinemia in seven normal volunteers during a 200-min hyperglycemic clamp (+ 9 mmol/l) carried out with [3-3H]glucose and indirect calorimetry. Hyperglycemia increased glucose uptake to 22.4 +/- 2.6 and 21.3 +/- 1.6 mumol.kg-1.min-1 with and without insulin replacement, respectively. Normoinsulinemia increased glucose oxidation (delta = + 4.5 +/- 0.6 mumol.kg-1.min-1) and nonoxidative glucose metabolism (delta = + 5.2 +/- 1.7 mumol.kg-1.min-1), whereas with insulinopenia, glucose oxidation did not change (delta = -0.3 +/- 0.6 mumol.kg-1.min-1), and nonoxidative glucose metabolism increased (delta = + 48.7 +/- 0.8 mumol.kg-1.min-1). Nonoxidative glucose metabolism was higher during insulinopenic (13.5 +/- 1.8 mumol.kg-1.min-1) than normoinsulinemic hyperglycemia (9.8 +/- 2.7 mumol.kg-1.min-1; P < 0.01). Plasma FFA concentration and lipid oxidation were higher with insulinopenia. Blood lactate and alanine concentrations were greater with normoinsulinemia. In conclusion: 1) hyperglycemia promotes glucose uptake by stimulating both nonoxidative and oxidative glucose disposal; 2) the ability of hyperglycemia to enhance total body glucose uptake is similar with and without normoinsulinemia; 3) although acute insulinopenia does not impair the ability of hyperglycemia to stimulate glucose uptake, it plays a critical role in determining the intracellular metabolic fate of glucose taken up in response to hyperglycemia.

Inhibition of lipolysis during acute GH exposure increases insulin sensitivity in previously untreated GH-deficient adults

2003 ◽  
pp. 511-519 ◽  
Author(s):  
M Segerlantz ◽  
M Bramnert ◽  
P Manhem ◽  
E Laurila ◽  
LC Groop
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Glucose Oxidation ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Acute Administration ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Double Blind ◽  
Lipolytic Effect

OBJECTIVE: Previous studies evaluating the lipolytic effect of GH have in general been performed in subjects on chronic GH therapy. In this study we assessed the lipolytic effect of GH in previously untreated patients and examined whether the negative effect of enhanced lipolysis on glucose metabolism could be counteracted by acute antilipolysis achieved with acipimox. METHODS: Ten GH-deficient (GHD) adults participated in four experiments each, during which they received in a double-blind manner: placebo (A); GH (0.88+/-0.13 mg) (B); GH+acipimox 250 mg b.i.d. (C); and acipimox b.i.d. (no GH) (D), where GH was given the night before a 2 h euglycemic, hyperinsulinemic clamp combined with infusion of [3-(3)H]glucose and indirect calorimetry. RESULTS: GH increased basal free fatty acid (FFA) levels by 74% (P=0.0051) and insulin levels by 93% (P=0.0051). This resulted in a non-significant decrease in insulin-stimulated glucose uptakes (16.61+/-8.03 vs 12.74+/-5.50 micromol/kg per min (s.d.), P=0.07 for A vs B). The rates of insulin-stimulated glucose uptake correlated negatively with the FFA concentrations (r=-0.638, P<0.0001). However, acipimox caused a significant improvement in insulin-stimulated glucose uptake in the GH-treated patients (17.35+/-5.65 vs 12.74+/-5.50 micromol/kg per min, P=0.012 for C vs B). The acipimox-induced enhancement of insulin-stimulated glucose uptake was mainly due to an enhanced rate of glucose oxidation (8.32+/-3.00 vs 5.88+/-2.39 micromol/kg per min, P=0.07 for C vs B). The enhanced rates of glucose oxidation induced by acipimox correlated negatively with the rate of lipid oxidation in GH-treated subjects both in basal (r=-0.867, P=0.0093) and during insulin-stimulated (r=-0.927, P=0.0054) conditions. GH did not significantly impair non-oxidative glucose metabolism (6.86+/-5.22 vs 8.67+/-6.65 micromol/kg per min, P=NS for B vs A). The fasting rate of endogenous glucose production was unaffected by GH and acipimox administration (10.99+/-1.98 vs 11.73+/-2.38 micromol/kg per min, P=NS for B vs A and 11.55+/-2.7 vs 10.99+/-1.98 micromol/kg per min, P=NS for C vs B). On the other hand, acipimox alone improved glucose uptake in the untreated GHD patients (24.14+/-8.74 vs 16.61+/-8.03 micromol/kg per min, P=0.0077 for D vs A) and this was again due to enhanced fasting (7.90+/-2.68 vs 5.16+/-2.28 micromol/kg per min, P=0.01 for D vs A) and insulin-stimulated (9.78+/-3.68 vs 7.95+/-2.64 micromol/kg per min, P=0.07 for D vs A) glucose oxidation. CONCLUSION: The study of acute administration of GH to previously untreated GHD patients provides compelling evidence that (i) GH-induced insulin resistance is mainly due to induction of lipolysis by GH; and (ii) inhibition of lipolysis can prevent the deterioration of insulin sensitivity. The question remains whether GH replacement therapy should, at least at the beginning of therapy, be combined with means to prevent an excessive stimulation of lipolysis by GH.

scholarly journals The fuel of the spleen. Studies using a new method for perfusing the rat spleen with whole blood

1989 ◽  
Vol 263 (2) ◽  
pp. 325-332 ◽  
Author(s):  
M A Mindham ◽  
P A Mayes
Keyword(s):  
Oxygen Consumption ◽  
Fatty Acid ◽  
Glucose Uptake ◽  
Whole Blood ◽  
Glucose Oxidation ◽  
The Other ◽  
Cell Populations ◽  
Total Oxygen ◽  
Total Glucose ◽  
Oxidation Of Glucose

1. An improved rat spleen perfusion is described incorporating a method of defibrination which avoids the use of heparin and enables the spleen to be perfused with rat blood for several hours at a haematocrit of 40% and for 12 h or more at a haematocrit of 20%. 2. Glucose oxidation accounted for 11.6% of the total oxygen consumption but this represented only 8% of total glucose uptake, which was largely converted to lactate and released into the perfusate. However, significant amounts of lactate were oxidized. These results can be explained by the presence of at least two cell populations, one emphasizing the anaerobic oxidation of glucose and the other aerobic metabolism, particularly of lactate. 3. Non-esterified fatty acid and 3-hydroxybutyrate, when available at physiological concentrations, were shown to be major oxidative fuels of the spleen. 4. Chylomicron triacylglycerol was hydrolysed readily and taken up, but not oxidized extensively.

scholarly journals Gastric inhibitory polypeptide and effects of glycation on glucose transport and metabolism in isolated mouse abdominal muscle

1998 ◽  
Vol 156 (2) ◽  
pp. 237-243 ◽  
Author(s):  
FP O'Harte ◽  
AM Gray ◽  
PR Flatt
Keyword(s):  
Glucose Uptake ◽  
Glucose Oxidation ◽  
Lactate Production ◽  
Fold Increase ◽  
Gastric Inhibitory Polypeptide ◽  
Abdominal Muscle ◽  
Reducing Conditions ◽  
Biological Effectiveness ◽  
First Time

This study investigates the effects of gastric inhibitory polypeptide (GIP) and glycated GIP (glucitol adduct of GIP) on glucose uptake and metabolism in muscle. Glycated GIP (molecular mass 5147.2 Da) was purified by HPLC following in vitro incubation under hyperglycaemic reducing conditions (24 h at pH 7.4). GIP (10(-10)-10(-8) mol/l) significantly stimulated (1.4- to 1.5-fold, P < 0.001) 2-deoxy-D-[1-3H]glucose uptake in abdominal muscle pieces from 3- to 5-week-old lean mice compared with control incubations (without GIP). This stimulatory effect on glucose uptake at 10(-10)-10(-9) mol/l was decreased by 13-20% following glycation of the peptide (P < 0.05). GIP (10(-9) and 10(-8) mol/l) induced a stepwise 1.4- to 1.7-fold increase (P < 0.01, P < 0.001 respectively) in [14C]glucose oxidation compared with controls. This effect on glucose oxidation was diminished by 32% with 10(-8) mol/l glycated GIP (P < 0.05). GIP (10(-9) and 10(-8) mol/l) induced a 1.4- to 1.8-fold increase in [14C]glucose incorporation into muscle glycogen (glycogenesis) compared with controls. Glycated GIP (10(-8) mol/l) exhibited a 41% decrease in glycogenic activity (P < 0.01). GIP (10(-10)-10(-8) mol/l) stimulated lactate production in isolated abdominal muscle (1.2- to 1.3-fold, P < 0.05); however glycated GIP did not exert a significant effect. This study demonstrates for the first time that GIP promotes glucose uptake, glucose oxidation and glycogenesis in muscle tissue. Furthermore, modification of GIP through glycation diminishes its biological effectiveness.

scholarly journals Effect of acetoacetate on glucose metabolism in the soleus and extensor digitorum longus muscles of the rat

1977 ◽  
Vol 162 (3) ◽  
pp. 557-568 ◽  
Author(s):  
E Z Maizels ◽  
N B Ruderman ◽  
M N Goodman ◽  
D Lau
Keyword(s):  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Glucose Oxidation ◽  
Extensor Digitorum Longus ◽  
Similar Rate ◽  
Extensor Digitorum ◽  
Lactate Release ◽  
Red Muscle ◽  
Slow Twitch ◽  
Fast Twitch

1. The effect of acetoacetate on glucose metabolism was compared in the soleus, a slow-twitch red muscle, and the extensor digitorum longus, a muscle composed of 50% fast-twitch red and 50% white fibres. 2. When incubated for 2h in a medium containing 5 mM-glucose and 0.1 unit of insulin/ml, rates of glucose uptake, lactate release and glucose oxidation in the soleus were 19.6, 18.6 and 1.47 micronmol/h per g respectively. Acetoacetate (1.7 mM) diminished all three rates by 25-50%; however, it increased glucose conversion into glycogen. In addition, it caused increases in tissue glucose, glucose 6-phosphate and fructose 6-phosphate, suggesting inhibition of phosphofructokinase. The concentrations of citrate, an inhibitor of phosphofructokinase, and of malate were also increased. 3. Rates of glucose uptake and lactate release in the extensor digitorum longus were 50-80% of those in the soleus. Acetoacetate caused moderate increases in tissue glucose 6-phosphate and possibly citrate, but it did not decrease glucose uptake or lactate release. 4. The rate of glycolysis in the soleus was approximately five times that previously observed in the perfused rat hindquarter, a muscle preparation in which acetoacetate inhibits glucose oxidation, but does not alter glucose uptake or glycolysis. A similar rate of glycolysis was observed when the soleus was incubated with a glucose-free medium. Under these conditions, tissue malate and the lactate/pyruvate ratio in the medium were decreased, and acetoacetate did not decrease lactate release or increase tissue citrate or glucose 6-phosphate. An intermediate rate of glycolysis, which was not decreased by acetoacetate, was observed when the soleus was incubated with glucose, but not insulin. 5. The data suggest that acetoacetate glucose inhibits uptake and glycolysis in red muscle under conditions that resemble mild to moderate exercise. They also suggest that the accumulation of citrate in these circumstances is linked to the rate of glycolysis, possibly through the generation of cytosolic NADH and malate formation.

scholarly journals Evaluation of the isolated perfused rat hindquarter for the study of muscle metabolism

1971 ◽  
Vol 124 (3) ◽  
pp. 639-651 ◽  
Author(s):  
N. B. Ruderman ◽  
C. R. S. Houghton ◽  
R. Hems
Keyword(s):  
Glucose Uptake ◽  
Nerve Stimulation ◽  
Ketone Bodies ◽  
Synthetic Medium ◽  
Lactate Production ◽  
Muscle Metabolism ◽  
High Rate ◽  
O2 Consumption ◽  
Glycerol Release

1. The metabolic integrity of a new isolated rat hindquarter preparation was studied. The hindquarter was perfused with a semi-synthetic medium containing aged human erythrocytes. More than 95% of the oxidative metabolism of the preparation was due to muscle, the remainder being due to bone, adipose tissue and, where present, skin. 2. Consumption of O2, glucose utilization, glycerol release and lactate production were similar in the presence and in the absence of the skin, indicating that the latter contributed little to the overall metabolism of the preparation. 3. After 40min of perfusion, tissue concentrations of creatine phosphate, ATP and ADP were similar to those found in muscle taken directly from intact animals. The muscle also appeared normal under the electron microscope. 4. The hindquarter did not lose K% to the medium during a 30min perfusion. In the presence of insulin it had a net K% uptake. 5. Insulin caused a sixfold increase in glucose uptake, stimulated O2 consumption by nearly 40% and depressed glycerol release to less than half the control value. 6. Bilateral sciatic-nerve stimulation caused severalfold increases in O2 consumption and lactate production. In the absence of insulin nerve stimulation also enhanced glucose uptake; in the presence of insulin it did not further increase the already high rate of glucose uptake. 7. Rates of lactate production and O2 consumption of the rat hindquarter in vivo and the isolated perfused hindquarter were very similar. 8. Ketone bodies were a major oxidative fuel in vivo of the hindquarter of a rat starved for 2 days. If the acetoacetate and 3-hydroxybutyrate removed by the tissue were completely oxidized, they would have accounted for 77% of the O2 consumption. 9. Acetoacetate accounted for 84% of the ketone bodies removed by the hindquarter in vivo even though its arterial concentration was half that of 3-hydroxybutyrate. 10. Similar rates of acetoacetate and 3-hydroxybutyrate utilization were observed in the perfused hindquarter. 11. Acetoacetate utilization by the perfused hindquarter was not diminished by the addition of either oleate or insulin to the perfusate. 12. Oxidation of glucose to CO2 accounted for less than 4% of the O2 consumed by the perfused hindquarter in both the presence and the absence of insulin. 13. The results indicate that the isolated perfused hindquarter is a useful tool for studying muscle metabolism. They also suggest that ketone bodies, if present in sufficient concentration, are the preferred oxidative fuel of resting muscle.

scholarly journals Differential adrenergic regulation of the gene expression of the β-adrenoceptor subtypes β1, β2 and β3 in brown adipocytes

2000 ◽  
Vol 347 (3) ◽  
pp. 643-651 ◽  
Author(s):  
Tore BENGTSSON ◽  
Barbara CANNON ◽  
Jan NEDERGAARD
Keyword(s):  
Gene Expression ◽  
Receptor Subtypes ◽  
Mrna Levels ◽  
Adrenergic Stimulation ◽  
Brown Adipocytes ◽  
Adrenergic Regulation ◽  
Receptor Mrna ◽  
Degradation Rates ◽  
Brown Adipose ◽  
Β Receptor

In brown adipocytes, fundamental cellular processes (cell proliferation, differentiation and apoptosis) are regulated by adrenergic stimulation, notably through β-adrenergic receptors. The presence of all three β-receptor subtypes has been demonstrated in brown adipose tissue. Due to the significance of the action of these receptors and indications that the subtypes govern different processes, the adrenergic regulation of the expression of the β1-, β2- and β3-adrenoceptor genes was examined in murine brown-fat primary cell cultures. Moderate levels of β1-receptor mRNA, absence of β2-receptor mRNA and high levels of β3-receptor mRNA were observed in mature brown adipocytes (day 6 in culture). Noradrenaline (norepinephrine) addition led to diametrically opposite effects on β1- (markedly enhanced expression) and β3-gene expression (full cessation of expression, as previously shown). β2-Gene expression was induced by noradrenaline, but only transiently (< 1 h). The apparent affinities (EC50) of noradrenaline were clearly different (7 nM for the β1-gene and≤ 1 nM for the β3-gene), as were the mediation pathways (solely via β3-receptors and cAMP for the β1-gene and via β3-receptors and cAMP, as well as via α1-receptors and protein kinase C, for the β3-gene). The half-lives of the corresponding mRNA species were very short but different (17 min for β1-mRNA and 27 min for β3-mRNA), and these degradation rates were not affected by noradrenaline, implying that the mRNA levels were controlled by transcription. Inhibition of protein synthesis also led to diametrically opposite effects on β1- and β3-gene expression, but - notably - these effects were congruent with the noradrenaline effects, implying that a common factor regulating β1-gene expression negatively and β3-gene expression positively could be envisaged. In conclusion, very divergent effects of adrenergic stimulation on the expression of the different β-receptor genes were found within one cell type, and no unifying concept of adrenergic control of β-receptor gene expression can be formulated, either concerning different cell types, or concerning the different β-receptor subtype genes.

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