Influences of AT1 receptor blockade on tissue metabolism in obese men

2006 ◽  
Vol 290 (1) ◽  
pp. R219-R223 ◽  
Author(s):  
Michael Boschmann ◽  
Stefan Engeli ◽  
Frauke Adams ◽  
Gabriele Franke ◽  
Friedrich C. Luft ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
At1 Receptor ◽  
Tissue Blood Flow ◽  
Receptor Blockade ◽  
Ang Ii ◽  
Adrenergic Stimulation ◽  
Tissue Metabolism ◽  
Interstitial Glucose ◽  
Glucose Supply

ANG II applied to the interstitial space influences carbohydrate and lipid metabolism in a tissue-specific fashion. Thus endogenous ANG II may have a tonic effect on tissue metabolism that could be reversed with ANG II type 1 (AT1) receptor blockade, particularly during adrenergic stimulation. We studied 14 obese men. They were treated for 10 days with the AT1 receptor blocker irbesartan or with placebo in a double-blind and crossover fashion. At the end of each treatment period, we assessed skeletal muscle and adipose tissue metabolism using the microdialysis technique. The ethanol dilution technique was applied to follow changes in tissue blood flow. Measurements were obtained at baseline and during application of incremental isoproterenol concentrations through the microdialysis catheter. Blood pressure decreased from 133 ± 3/84 ± 3 to 128 ± 3/79 ± 2 mmHg for systolic and diastolic blood, respectively ( P = 0.02 and 0.006, respectively) with AT1 receptor blockade. Isoproterenol perfusion caused a dose-dependent increase in dialysate glycerol in adipose tissue and in skeletal muscle. Irbesartan slightly reduced the isoproterenol-induced glycerol response in adipose tissue ( P < 0.05 by ANOVA). Ethanol ratio, interstitial glucose supply, and lactate production in adipose tissue and skeletal muscle were similar with placebo and irbesartan. We conclude that AT1 receptor blockade in obese men does not reveal a major tonic ANG II effect on interstitial glucose supply, lipolysis, or glycolysis in skeletal muscle, either at rest or during β-adrenergic stimulation. Endogeneous ANG II may slightly increase adipose tissue lipolysis. The mechanism may promote the redistribution of triglycerides from adipose tissue toward other organs.

scholarly journals Total Forearm Blood Flow as an Indicator of Skeletal Muscle Blood Flow: Effect of Subcutaneous Adipose Tissue Blood Flow

1994 ◽  
Vol 87 (5) ◽  
pp. 559-566 ◽  
Author(s):  
E. E. Blaak ◽  
M. A. van Baak ◽  
G. J. Kemerink ◽  
M. T. W. Pakbiers ◽  
G. A. K. Heidendal ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Forearm Blood Flow ◽  
Muscle Blood Flow ◽  
Tissue Blood Flow ◽  
Adipose Tissue Blood Flow ◽  
Flow Through ◽  
Subcutaneous Adipose

1. In studying forearm skeletal muscle substrate exchange, an often applied method for estimating skeletal muscle blood flow is strain gauge plethysmography. A disadvantage of this method is that it only measures total blood flow through a segment of forearm and not the flow through the individual parts such as skin, adipose tissue and muscle. 2. In the present study the contribution of forearm subcutaneous adipose tissue blood flow to total forearm blood flow was evaluated in lean (% body fat 17.0 ± 2.2) and obese males (% body fat 30.9 ± 1.6) during rest and during infusion of the non-selective β-agonist isoprenaline. Measurements were obtained of body composition (hydrostatic weighing), forearm composition (magnetic resonance imaging) and of total forearm (venous occlusion plethysmography), skin (skin blood flow, laser Doppler), and subcutaneous adipose tissue blood flow (133Xe washout technique). 3. The absolute forearm area and the relative amount of fat (% of forearm area) were significantly higher in obese as compared to lean subjects, whereas the relative amounts of muscle and skin were similar. 4. During rest, the percentage contribution of adipose tissue blood flow to total forearm blood flow was significantly higher in lean compared with obese subjects (19 vs 12%, P < 0.05), whereas there were no differences in percentage contribution between both groups during isoprenaline infusion (10 vs 13%). Furthermore, the contribution of adipose tissue blood flow to total forearm blood flow was significantly lower during isoprenaline infusion than during rest in lean subjects (P < 0.05), whereas in the obese this value was similar during rest and during isoprenaline infusion. 5. In conclusion, although the overall contribution of adipose tissue blood flow to total forearm blood flow seems to be relatively small, the significance of this contribution may vary with degree of adiposity. Calculations on the contribution of adipose tissue blood flow and SBF to total forearm blood flow indicate that the contribution of non-muscular flow to total forearm blood flow may be of considerable importance and may amount in lean subjects to 35–50% of total forearm blood flow in the resting state.

Local histamine H1- and H2-receptor blockade reduces postexercise skeletal muscle interstitial glucose concentrations in humans

2010 ◽  
Vol 35 (5) ◽  
pp. 617-626 ◽  
Author(s):  
Thomas K. Pellinger ◽  
Grant H. Simmons ◽  
David A. MacLean ◽  
John R. Halliwill
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Vastus Lateralis ◽  
Receptor Activation ◽  
Peak Oxygen Uptake ◽  
Vastus Lateralis Muscle ◽  
Receptor Blockade ◽  
Glucose Levels ◽  
Interstitial Glucose ◽  
The Impact

Elevated blood flow can potentially influence skeletal muscle glucose uptake, but the impact of postexercise hyperemia on glucose availability to skeletal muscle remains unknown. Because postexercise hyperemia is mediated by histamine H1- and H2-receptors, we tested the hypothesis that postexercise interstitial glucose concentrations would be lower in the presence of combined H1- and H2-receptor blockade. To this end, 4 microdialysis probes were inserted into the vastus lateralis muscle of 14 healthy subjects (21–27 years old) immediately after 60 min of either upright cycling at 60% peak oxygen uptake (exercise, n = 7) or quiet rest (sham, n = 7). Microdialysis probes were perfused with a modified Ringer’s solution containing 3 mmol·L–1 glucose, 5 mmol·L–1 ethanol, and [6-3H] glucose (200 disintegrations·min–1·μL–1). Two sites (blockade) received both H1- and H2-receptor antagonists (1 mmol·L–1 pyrilamine and 3 mmol·L–1 cimetidine) and 2 sites (control) did not receive antagonists. Ethanol outflow/inflow ratios (an inverse surrogate of local blood flow) were higher in blockade sites than in control sites following exercise (p < 0.05), whereas blockade had no effect on ethanol outflow/inflow ratios following sham (p = 0.80). Consistent with our hypothesis, during 3 of the 5 dialysate collection periods, interstitial glucose concentrations were lower in blockade sites vs. control sites following exercise (p < 0.05), whereas blockade had no effect on interstitial glucose concentrations following sham (p = 0.79). These findings indicate that local H1- and H2-receptor activation modulates skeletal muscle interstitial glucose levels during recovery from exercise in humans and suggest that the availability of glucose to skeletal muscle is enhanced by postexercise hyperemia.

Adipose tissue function in the insulin-resistance syndrome

2005 ◽  
Vol 33 (5) ◽  
pp. 1045-1048 ◽  
Author(s):  
F. Karpe ◽  
G.D. Tan
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Blood Flow ◽  
Adipose Tissue ◽  
Blood Glucose Concentration ◽  
Insulin Resistance Syndrome ◽  
The Body ◽  
Tissue Blood Flow ◽  
Main Function ◽  
Adipose Tissue Blood Flow

Insulin resistance is often seen as a consequence of obesity and there are several possible links between adipose tissue function and insulin resistance determined in other organs such as skeletal muscle or liver. One such link is the regulation of NEFA (non-esterified fatty acid) delivery to the rest of the body. Simplistically, an expanded adipose tissue mass delivers more NEFA to the systemic circulation and these fatty acids compete for substrate utilization in skeletal muscle, which in turn reduces glucose utilization. This increases blood glucose concentration and provides the stimulus for increased insulin secretion and hyperinsulinaemia is a key feature of the insulin-resistance syndrome. However, there is abundant evidence that adipose tissue is exquisitely insulin sensitive and hyperinsulinaemia may therefore lead to a constant lipolytic inhibition in adipose tissue. Consequently, the main function of adipose tissue, to rapidly switch between fat uptake and fat release, will be hampered. Adipose tissue blood flow is the conveyor of signals and substrates to and from the adipose tissue. In healthy people adipose tissue blood flow is much enhanced by food intake, whereas in insulin-resistant subjects this response is blunted. This is another facet of unresponsiveness of adipose tissue in the insulin-resistance syndrome.

scholarly journals Metabolic characteristics of human subcutaneous abdominal adipose tissueafter overnight fast

2012 ◽  
Vol 302 (4) ◽  
pp. E468-E475 ◽  
Author(s):  
Keith N. Frayn ◽  
Sandy M. Humphreys
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Glucose Uptake ◽  
Human Adipose Tissue ◽  
Tissue Blood Flow ◽  
Nonesterified Fatty Acids ◽  
Abdominal Adipose Tissue ◽  
Adipose Tissue Metabolism ◽  
Tissue Metabolism ◽  
Subcutaneous Abdominal Adipose Tissue

Subcutaneous abdominal adipose tissue is one of the largest fat depots and contributes the major proportion of circulating nonesterified fatty acids (NEFA). Little is known about aspects of human adipose tissue metabolism in vivo other than lipolysis. Here we collated data from 331 experiments in 255 healthy volunteers over a 23-year period, in which subcutaneous abdominal adipose tissue metabolism was studied by measurements of arterio-venous differences after an overnight fast. NEFA and glycerol were released in a ratio of 2.7:1, different ( P < 0.001) from the value of 3.0 that would indicate no fatty acid re-esterification. Fatty acid re-esterification was 10.2 ± 1.4%. Extraction of triacylglycerol (TG) (fractional extraction 5.7 ± 0.4%) indicated intravascular lipolysis by lipoprotein lipase, and this contributed 21 ± 3% of the glycerol released. Glucose uptake (fractional extraction 2.6 ± 0.3%) was partitioned around 20–25% for provision of glycerol 3-phosphate and 30% into lactate production. There was release of lactate and pyruvate, with extraction of the ketone bodies 3-hydroxybutyrate and acetoacetate, although these were small numerically compared with TG and glucose uptake. NEFA release (expressed per 100 g tissue) correlated inversely with measures of fat mass (e.g., with BMI, rs= −0.24, P < 0.001). We examined within-person variability. Systemic NEFA concentrations, NEFA release, fatty acid re-esterification, and adipose tissue blood flow were all more consistent within than between individuals. This picture of human adipose tissue metabolism in the fasted state should contribute to a greater understanding of adipose tissue physiology and pathophysiology.

Lipolysis and Lactate Production in Human Skeletal Muscle and Adipose Tissue following Glucose Ingestion

1998 ◽  
Vol 94 (1) ◽  
pp. 71-77 ◽  
Author(s):  
Daniëlle A. J. M. Kerckhoffs ◽  
Peter Arner ◽  
Jan Bolinder
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Adipose Tissue ◽  
Muscle Blood Flow ◽  
Lactate Production ◽  
Tissue Blood Flow ◽  
Oral Glucose ◽  
Glucose Load ◽  
Carbohydrate Ingestion ◽  
Glucose Ingestion

1. Using microdialysis, we compared lipolysis, as well as the production of lactate, in human adipose tissue and muscle after the ingestion of carbohydrate. 2. The absolute concentrations of glycerol and lactate were measured in subcutaneous adipose tissue, skeletal muscle and arterialized venous blood in eight normal subjects during basal conditions and 4 h after a 75 g oral glucose load. Nutritive blood flow in muscle and adipose tissue was monitored simultaneously with the microdialysis ethanol clearance technique. 3. At baseline, the concentrations of glycerol in adipose tissue and in muscle were about 7 times and about 2.5 times higher respectively than those in plasma. After glucose ingestion, the changes in glycerol concentrations differed significantly between the three compartments (P < 0.0001). In plasma and adipose tissue, the concentrations decreased rapidly and markedly, but returned to baseline levels after 4 h. In muscle, the decrease in glycerol was less pronounced and more protracted. 4. At baseline, the concentrations of lactate in muscle and in adipose tissue were about 3 times and about 1.5 times higher respectively than those in plasma. After the ingestion of glucose, the levels increased transiently in similar ways in muscle, adipose tissue and plasma. The differences in absolute lactate concentrations between the three compartments were maintained after the glucose load (P < 0.001). 5. Adipose tissue blood flow increased transiently after glucose ingestion, whereas muscle blood flow remained unchanged. 6. Both muscle and adipose tissue are a source of glycerol and lactate release during basal conditions and after glucose ingestion. The regulation of lactate production, but not of lipolysis, after carbohydrate ingestion is similar in the two tissues.

scholarly journals Insulin-sensitizing effects of dietary resistant starch and effects on skeletal muscle and adipose tissue metabolism

2005 ◽  
Vol 82 (3) ◽  
pp. 559-567 ◽  
Author(s):  
M Denise Robertson ◽  
Alex S Bickerton ◽  
A Louise Dennis ◽  
Hubert Vidal ◽  
Keith N Frayn
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Resistant Starch ◽  
Adipose Tissue Metabolism ◽  
Tissue Metabolism

Assessment of transcapillary glucose exchange in human skeletal muscle and adipose tissue

2003 ◽  
Vol 285 (2) ◽  
pp. E241-E251 ◽  
Author(s):  
Werner Regittnig ◽  
Martin Ellmerer ◽  
Günter Fauler ◽  
Gerald Sendlhofer ◽  
Zlatko Trajanoski ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Human Skeletal Muscle ◽  
Human Subjects ◽  
Quadriceps Muscle ◽  
Model Parameters ◽  
Interstitial Glucose ◽  
Normal Human ◽  
Dynamic Relationships ◽  
Subcutaneous Adipose

We studied the kinetics of glucose exchange between plasma and interstitial fluid (ISF) in human skeletal muscle and adipose tissue under fasting conditions. Five normal human subjects received an intravenous [6,6-2H2]glucose infusion in a prime-continuous fashion. During the tracer infusion, the open-flow microperfusion technique was employed to frequently sample ISF from quadriceps muscle and subcutaneous adipose tissue. The tracer glucose kinetics observed in muscle and adipose tissue ISF were found to be well described by a capillary-tissue exchange model. As a measure of transcapillary glucose exchange efficiency, the 95% equilibrium time was calculated from the identified model parameters. This time constant was similar for skeletal muscle and adipose tissue (28.6 ± 3.2 vs. 26.8 ± 3.6 min; P = 0.60). Furthermore, we found that the (total) interstitial glucose concentration was significantly lower ( P < 0.01) in muscle (3.32 ± 0.46 mmol/l) and adipose tissue (3.51 ± 0.17 mmol/l) compared with arterialized plasma levels (5.56 ± 0.13 mmol/l). Thus the observed gradients and dynamic relationships between plasma and ISF glucose in muscle and adipose tissue provide evidence that transcapillary exchange of glucose is limited in these two tissues under fasting conditions.

Predominant activation of endothelin-dependent cardiac hypertrophy by norepinephrine in rat left ventricle

2002 ◽  
Vol 282 (5) ◽  
pp. R1389-R1394 ◽  
Author(s):  
Lutz Moser ◽  
Jörg Faulhaber ◽  
Rudolf J. Wiesner ◽  
Heimo Ehmke
Keyword(s):  
Gene Expression ◽  
Left Ventricle ◽  
Aortic Stenosis ◽  
Cardiac Hypertrophy ◽  
Left Ventricular ◽  
Receptor Blockade ◽  
Ang Ii ◽  
Adrenergic Stimulation ◽  
Adult Rats ◽  
Primary Stimulus

Locally released endothelin (ET)-1 has been recently identified as an important mediator of cardiac hypertrophy. It is still unclear, however, which primary stimulus specifically activates ET-dependent signaling pathways. We therefore examined in adult rats ( n = 51) the effects of a selective ETA receptor antagonist in experimental models of cardiac hypertrophy, in which myocardial growth is predominantly initiated by a single primary stimulus. Rats were exposed to mechanical overload (ascending aortic stenosis), increased levels of circulating ANG II (ANG II infusion combined with hydralazine), or adrenergic stimulation (infusion of norepinephrine in a subpressor dose) for 7 days. All experimental treatments significantly increased left ventricular weight/body weight ratios compared with untreated rats, whereas systolic left ventricular peak pressure was increased only after ascending aortic stenosis. ETA receptor blockade exclusively reduced norepinephrine-induced cardiac hypertrophy and atrial natriuretic peptide gene expression. Blood pressure levels and heart rates remained unaffected during ETA receptor blockade in all experimental groups. These data indicate that in rat left ventricle, the ET-dependent signaling pathway leading to early development of cardiac hypertrophy and fetal gene expression is primarily activated by norepinephrine.

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