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Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2007-1313
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The Journal of Clinical Endocrinology & Metabolism Vol. 93, No. 1 240-246
Copyright © 2008 by The Endocrine Society

Catecholamine Regulation of Local Lactate Production in Vivo in Skeletal Muscle and Adipose Tissue: Role of β-Adrenoreceptor Subtypes

Veronica Qvisth, Eva Hagström-Toft, Staffan Enoksson and Jan Bolinder

Department of Medicine (V.Q., E.H.-T., J.B.), Karolinska University Hospital-Huddinge, Karolinska Institutet, SE-141 86 Stockholm, Sweden; and Department of Vascular Surgery (S.E.), Karolinska University Hospital-Solna, Karolinska Institutet, SE-171 76 Stockholm, Sweden

Address all correspondence and requests for reprints to: Veronica Qvisth, M.D., Ph.D., Diabetesmottagningen, Ersta Hospital, Box 4622, S-116 91 Stockholm, Sweden. E-mail: veronica.qvisth{at}ki.se.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
Context: The regulation of lactate production in skeletal muscle (SM) and adipose tissue (AT) is not fully elucidated.

Objective: Our objective was to investigate the catecholamine-mediated regulation of lactate production and blood flow in SM and AT in healthy, normal-weight subjects by using microdialysis.

Methods: First, lactate levels in SM and AT were measured during an iv norepinephrine infusion (n = 11). Local blood flow was determined with the 133Xe-clearance technique. Second, muscle lactate was measured during hypoglycemia and endogenous epinephrine stimulation (n = 12). Third, SM was perfused with selective β1–3-adrenoreceptor agonists in situ (n = 8). Local blood flow was measured with the ethanol perfusion technique.

Results: In response to iv norepinephrine, the fractional release of lactate (difference between tissue and arterial lactate) increased by 40% in SM (P = 0.001), whereas remaining unchanged in AT. Blood flow decreased by 40% in SM (P < 0.005) and increased by 50% in AT (P < 0.05). In response to hypoglycemia, epinephrine increased 10-fold, and the fractional release of lactate in SM doubled (P < 0.0001). The blood flow remained unchanged. The β2-agonist, terbutaline, caused a marked concentration-dependent increase of muscle lactate and blood flow (P < 0.0001). The β1-agonist, dobutamine, induced a discrete increase of muscle lactate (P < 0.0001), and the blood flow remained unchanged. The β3-agonist, CPG 12177, did not affect muscle lactate or blood flow.

Conclusions: Catecholamines stimulate lactate production in SM, but not in AT. In SM, the β2-adrenoreceptor is the most important β-adrenergic receptor subtype in the regulation of lactate production.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
Lactate is an important metabolic intermediate that represents a significant fuel source and gluconeogenetic precursor (1, 2). Moreover, several studies imply that increased whole-body lactate turnover may be of importance in the development of insulin resistance, probably due to accelerated hepatic gluconeogenesis (3, 4, 5, 6, 7). Although skeletal muscle (SM) is considered to be the major site of lactate production, it is well established that adipose tissue (AT) is also a significant source of lactate release (8, 9, 10, 11, 12). In a recent study, we found that lactate release from the enlarged AT in obesity can possibly explain the augmented lactate turnover seen in insulin resistance and obesity (8).

With regard to the hormonal regulation, ourselves and others have shown that lactate production in AT is stimulated by insulin (9, 10, 11, 12, 13). By contrast, in SM insulin-induced lactate release appears to be due to vascular effects rather than increased myocellular lactate production (8).

The effects of catecholamines and the sympathetic nervous system on local lactate production in SM and AT are less well characterized. The catecholamines are generally known to have insulin-antagonistic effects on glucose utilization, leading to peripheral insulin resistance and rapid increase in plasma glucose concentration in "fight or flight" situations (14, 15). During exercise, epinephrine is demonstrated to increase lactate production via activation of glycogenolysis in SM (16, 17). However, the effects of local catecholamine stimulation on lactate release in SM and AT are not clear.

Therefore, the aim of this study was to investigate tissue-specific effects of catecholamine stimulation on lactate production and blood flow rates in SM and AT. First, microdialysis and the 133Xe-clearance technique were used to measure interstitial lactate and the rates of blood flow in AT and SM during a norepinephrine infusion. To explore further the adrenergic regulation of lactate production in SM, interstitial lactate and local blood flow were assessed in muscle during exposure to endogenously secreted catecholamines (mainly epinephrine) in response to insulin-induced hypoglycemia. In addition, in a third subset of experiments, the muscle tissue was locally stimulated with selective β1–3-adrenoreceptor agonists, and the local blood flow was measured with the ethanol perfusion technique.


   Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
Subjects

In total, 31 healthy, drug-free volunteers were investigated (13 men, 18 women; 29 ± 2 yr; body mass index 23.3 ± 0.8 kg/m2). Each subject participated in only one of the three substudies. All of them performed regular physical activity, but not at an athletic level. The subjects gave their informed consent, and the study was approved by the Ethics Committee of the Karolinska Institute.

Microdialysis

The principle of microdialysis has been described in detail previously (18). The microdialysis catheter (CMA/60; CMA Microdialysis, Stockholm, Sweden) consists of a semipermeable membrane (30 x 0.62-mm, molecular mass cutoff 20 kDa) connected to the end of a double-lumen polyurethane tube. The probe is inserted into the tissue and is continuously perfused using a precision pump (CMA/100 microinjection pump; CMA Microdialysis) with a sterile solution. An exchange of metabolites occurs over the microdialysis membrane, and the composition of the outflow solution reflects the extracellular fluid.

Study protocol

All subjects were investigated in the supine position after an overnight fast. The experiments began at 0730 h.

Systemic norepinephrine administration (n = 11) A retrograde catheter (Venflon; BD, Franklin Lakes, NJ) was inserted into a dorsal hand vein. The hand was placed in an air-heated box (63 C) for sampling of arterialized venous plasma. In the cubital vein of the contralateral arm, a second Venflon catheter was placed for infusion of norepinephrine. After superficial skin anesthesia (EMLA; Astra, Södertälje, Sweden), microdialysis catheters were inserted in the periumbilical abdominal sc AT and in the medial part of the gastrocnemius muscle. The catheters were continuously perfused with Ringer’s solution (Apoteksbolaget, Umeå, Sweden), containing 147 mmol/liter Na, 4 mmol/liter K, 2.3 mmol/liter Ca, and 156 mmol/liter Cl, at a flow rate of 0.3 µl/min. This flow rate has given almost complete recovery (>95%) of lactate in SM and AT (11).

After an equilibration period of 120 min, the dialysate samples were collected in 15-min fractions for analysis of lactate. Plasma samples were drawn in the middle of each dialysate fraction for determination of lactate and glucose. After 60-min basal sampling, the subjects were given an iv norepinephrine infusion (0.56 nmol · kg lean body mass–1 · min–1) (Apoteksbolaget) for 75 min, followed by a 45-min recovery period. It has previously been shown that the circulating norepinephrine concentration is increased to the upper physiological level with this protocol (19). Concentrations of catecholamines (epinephrine and norepinephrine) were determined at regular intervals during the procedure.

The tissue blood flow was assessed with the 133Xe-clearance technique, as described in detail previously (20). In AT, 133Xe (1.0 MBq in 0.1 ml saline; Mallinckrodt, Petten, The Netherlands) was injected percutaneously into the paraumbilical sc tissue, opposite of the microdialysis catheter, 30 min before the start of the baseline period. After 30-min equilibration, the clearance rate was monitored by a scintillation detector (Mediscint; Oakfield Instruments Ltd., Oxford, UK) continuously throughout the study period. In SM, the 133Xe decay curve becomes multiexponential over time, and the blood flow has to be calculated from the initial mono-exponential part of the 133Xe washout curve (21). Therefore, 133Xe (0.3 MBq in 0.1 ml saline) was injected twice in the contralateral gastrocnemius muscle. The first injection was given after 40-min basal sampling. The second injection was given after 45-min noradrenaline infusion. Recordings were started 5 min after the injection and continued for 30 min. The first 10 min of the SM decay curve was used for calculations. AT and muscle blood flow were calculated according to the following equation:

Formula
where TBF denotes tissue blood flow, k denotes the rate constant of the decay of the residual activity, and {lambda} the tissue-to-blood partition coefficient. The values for {lambda} were set at 10 ml/g for AT and 0.7 ml/g for muscle (20, 22).

Hyperinsulinemic hypoglycemic clamp (n = 12) Teflon catheters (Venflon) were inserted, as described in the systemic norepinephrine administration experiment, into a dorsal hand vein and in the cubital vein of the contralateral arm for sampling of arterialized venous plasma and for infusion of insulin and glucose. Two microdialysis catheters were inserted into the gastrocnemius muscle. Qualitative estimations of variations in local tissue blood flow were made by the ethanol perfusion technique (23). Ethanol, which is not locally degraded and does not affect tissue metabolism, was added to the perfusate solution as a flow marker. Changes in the ethanol concentration ratio (out- vs. in-going ethanol concentration) reflect changes in the local blood flow. This technique has been validated against the 133Xe-clearance technique in SM, and it can detect changes in local blood flow that are more than 50% (23).

One catheter was perfused at 0.3 µm/min with Ringer’s solution alone, and the other catheter was perfused at 2.0 µm/min with Ringer’s solution supplemented with ethanol (50 mM) for estimation of tissue blood flow variations. The perfusate from each microdialysis catheter was collected in 15-min fractions for analysis of lactate or ethanol.

After a 120-min equilibration phase, and after 45-min basal sampling, an iv insulin infusion (0.15 U/kg body wt; Actrapid; NovoNordisk, Copenhagen, Denmark) was given over 60 min. After approximately 30 min, the concentration of blood glucose had decreased to approximately 2.5 mmol/liter, and a variable glucose infusion (200 mg/ml) was started to maintain the blood glucose at 2.5 mmol/liter for 30 min. The insulin infusion was then terminated, and blood glucose was allowed to recover gradually to the fasting level during the following 120 min. Blood glucose was monitored bedside for adjustments of the glucose infusion rate (Hemocue, Ángelholm, Sweden). Plasma samples were drawn in the middle of each dialysate sampling period for analysis of plasma lactate. Plasma catecholamine and insulin concentrations were determined at regular intervals during the procedure.

β-Adrenoreceptor stimulation in situ (n = 8) In separate experiments local stimulation by β-adrenoreceptor selective agonists were studied in SM tissue in situ. Four microdialysis catheters were inserted into the gastrocnemius muscle, two in each leg, and perfused with Ringer’s solution supplemented with ethanol (50 mM) at a flow rate of 2 µl/min. After 45-min baseline sampling, β-adrenoreceptor specific agonists were added to the perfusate of three catheters: the β1-selective agonist dobutamine (Eli Lilly, Indianapolis, IN) in one catheter; the β2-selective agonist terbutaline (Draco, Lund, Sweden) in the second catheter; and the β3-selective agonist CGP12,177 (Ciba-Geigy, Basel, Switzerland) in the third catheter. The initial concentration was 10–6 M, and after 90 min, it was increased to 10–5 M, and the sampling continued for another 90 min. The fourth catheter was used as a control and perfused throughout the experiment with the Ringer’s-ethanol solution only. The dialysate samples for analysis of lactate and ethanol were collected in 15-min fractions.

Biochemical analysis

Dialysate lactate was determined with an enzymatic fluorometric method, using a tissue sample analyzer (CMA/600; CMA Microdialysis). Dialysate ethanol was determined with an enzymatic spectrophotometric method (24). Plasma lactate was determined by an enzymatic fluorometric method (25). Plasma catecholamines were measured with high-performance chromatography with electrochemical detection (26). Plasma free insulin was determined by a commercial RIA (Pharmacia, Uppsala, Sweden). Plasma glucose was analyzed using the hospital’s routine clinical laboratory.

Statistics

The results are expressed as means ± SE Variations over time in the same compartments were evaluated with one-factor ANOVA, corrected for repeated measurements. Comparisons over time between groups were analyzed with two-factor repeated measurement ANOVA. Factorial ANOVA was used for comparison between groups not involving time. Post hoc analysis was performed by Scheffé’s test. The Student’s paired t test was used when different time segments were compared. Correlation analysis was performed to evaluate the relationship between two variables. A value of P < 0.05 was considered statistically significant. A statistical software package (StatView version 5.0 for the Macintosh system; Berkeley, CA) was used for all the statistical calculations.


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
Systemic norepinephrine stimulation

The concentrations of norepinephrine in plasma were 1.0 ± 0.1 nmol/liter at baseline. Plasma norepinephrine rapidly increased and remained at a steady-state level of 9.6 ± 0.9 nmol/liter throughout the 75-min period of iv norepinephrine infusion. The values immediately returned to basal levels when the infusion was stopped. Plasma epinephrine was below the detection limit of this method (0.3 nmol/liter) throughout the study period.

In the postabsorptive state, the lactate levels were three times higher in SM, and twice as high in AT compared with plasma (P < 0.0001, factorial ANOVA; Fig. 1AGo). In plasma a discrete but significant elevation of the lactate concentrations by approximately 15% was seen throughout the norepinephrine infusion (P < 0.0001, one factor ANOVA for repeated measurements). This was paralleled by a comparable 15% elevation of plasma glucose concentrations (P < 0.0001, one factor ANOVA for repeated measurements; Fig. 1AGo). In the SM the lactate values increased by about 30%. The increase in muscle lactate began immediately after the noradrenaline infusion started, peaked at 25 min, and then gradually decreased and were below basal values at the end of the recovery period (P < 0.0001, one factor ANOVA for repeated measurements). There were no significant changes in AT lactate in response to the norepinephrine infusion.


Figure 1
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  		FIG. 1. Effect of iv norepinephrine (NA) infusion on: lactate in arterialized venous plasma, AT and gastrocnemius muscle, and glucose in arterialized venous plasma (A); and the difference between the interstitial tissue lactate concentration and the arterialized venous plasma lactate level (I-A difference) in AT and gastrocnemius muscle (B). Values are expressed as mean ± SE.

 
The fractional release of lactate (i.e. the difference between the tissue and arterial lactate concentrations) is presented in Fig. 1BGo. In SM a significant increase of the interstitial-plasma difference was seen in response to norepinephrine stimulation (P = 0.001, one factor ANOVA for repeated measurements). The kinetics of the fractional lactate release followed the same pattern as the absolute lactate curve in SM. The fractional lactate concentrations were increased by approximately 40% at the peak after 25-min norepinephrine infusion. In AT there were no significant changes in fractional lactate release during the study period.

In SM the blood flow rate decreased from 1.89 ± 0.35 ml · min–1 · 100 g–1 during the basal period to 1.11 ± 0.17 ml · min–1 · 100 g–1 during the norepinephrine infusion (P < 0.005, Student’s t test). In AT there was a transient increase of the blood flow rates in response to norepinephrine. The basal blood flow rates 3.78 ± 0.75 ml · min–1 · 100 g–1 increased to 5.73 ± 0.93 ml · min–1 · 100 g–1 at 25-min norepinephrine infusion and then gradually returned to basal levels (P < 0.05, one factor ANOVA for repeated measurements).

Hyperinsulinemic hypoglycemic clamp

The concentrations of glucose, insulin, and catecholamines during the experiment are shown in Table 1Go. Plasma glucose concentrations gradually decreased during the first 30-min insulin infusion and then stayed at a stable hypoglycemic level throughout the remaining 30-min infusion. After withdrawal of the insulin infusion, plasma glucose successively returned to initial values. The peak values of both endogenous catecholamines occurred 50–70 min after the insulin infusion was started. The epinephrine concentrations increased more than 10-fold above the baseline, and they were still significantly increased 1 h after the end of the insulin infusion (P < 0.01, Student’s paired t test). For norepinephrine the increase was barely 2-fold (P < 0.001, Student’s paired t test), and the values had returned to baseline 1 h after the insulin infusion was stopped.


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  		TABLE 1. Glucose, insulin, and catecholamine concentrations in plasma during hyperinsulinemic hypoglycemic clamp (n = 12)

 
The fractional release of lactate in SM is presented in Fig. 2Go. During the initial period of the insulin infusion, the fractional lactate release remained unchanged. In response to hypoglycemia, the difference between the interstitial tissue lactate concentration and the arterialized venous plasma lactate level increased significantly (P < 0.0001, one-way ANOVA for repeated measurements), and the increase coincided with the peak values of the catecholamines. The fractional release of lactate from the muscle tissue was almost doubled approximately 35 min after the hypoglycemic nadir and remained elevated throughout the study period.


Figure 2
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  		FIG. 2. The difference between the interstitial tissue lactate concentration and the arterialized venous plasma lactate level (I-A difference) in gastrocnemius muscle during a hyperinsulinemic hypoglycemic clamp (n = 12). Values are expressed as mean ± SE.

 
No significant changes in SM ethanol outflow to inflow ratios, as calculated as percent change from basal values, were registered (data not shown).

β-Adrenoreceptor stimulation in situ

The SM lactate increased in a concentration-dependent manner when the β1- and β2-selective adrenoreceptor agonists dobutamine and terbutaline were perfused (P < 0.0001, one-factor ANOVA for repeated measurements; Fig. 3Go). However, the increase in muscle lactate was significantly higher when terbutaline was added to the perfusate than when dobutamine was added (P < 0.0001, two-factor ANOVA for repeated measurements). The lactate concentration was approximately 180% of baseline at the lower β2-agonist concentration and approximately 245% of baseline at the higher concentration of terbutaline (P < 0.0001, ANOVA). The corresponding muscle lactate at 10–6 and 10–5 M dobutamine was approximately 130 and 160% of basal levels, respectively (P < 0.0001, ANOVA). There were no changes in lactate concentration when the β3-selective agonist CPG 12,177 was perfused. In the control experiment (Ringer’s solution only), the interstitial lactate remained unchanged.


Figure 3
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  		FIG. 3. Effect of β-adrenoreceptor agonists on interstitial lactate in SM. Four microdialysis catheters were implanted into gastrocnemius muscle in eight healthy subjects. After baseline sampling, increasing concentrations of selective β-adrenoreceptor agonists were added to the perfusate: β1-agonist dobutamine, β2-agonist terbutaline, and β3-agonist GCP-12,177. The fourth catheter served as a control and was continuously perfused with Ringer-ethanol solution alone. Values are expressed as mean ± SE.

 
The results of the ethanol clearance are demonstrated in Table 2Go. The ethanol ratio declined in a concentration-dependent manner, indicating increase in local muscle blood flow, when β2-agonist terbutaline was added to the perfusate (one-factor ANOVA, P < 0.0001, 10–6 vs. 10–5 M, P < 0.05, using post hoc analysis). The ethanol ratio in the β1- and β3-adrenoreceptor agonist experiments did not differ from the control. Using individual data, there was no significant relationship between the interstitial lactate levels and the ethanol ratios in the terbutaline experiments (r = –0.2; P = NS).


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  		TABLE 2. Effect of β-agonist on tissue blood flow

 

   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
In the present study, we investigated the effects of the endogenous catecholamines and the β-adrenergic regulation of lactate metabolism in human SM and AT in vivo by using microdialysis. In the first type of experiment, norepinephrine was delivered systemically by an iv infusion. Norepinephrine is essentially a neurotransmitter, and the circulating levels are considered to be a spillover of the synaptic cleft concentrations. Unfortunately, the true, absolute interstitial concentrations of norepinephrine in the tissues cannot be measured with microdialysis. However, the concentrations of norepinephrine in plasma increased approximately 10 times above basal values to a level normally seen at high intensity physiological exercise (27) and that previously have been demonstrated to stimulate markedly the lipolysis in AT (28). This strongly indicates that the local tissue concentrations of norepinephrine also were at physiological levels.

Our findings show that norepinephrine stimulates lactate production in SM, but not in AT. In contrast, we have earlier reported the opposite effect of norepinephrine on the lipolytic activity, in which a stimulation of lipolysis by norepinephrine was seen in AT, but not in SM (28). This suggests that in situations in which the sympathetic nerve activity is increased, the lactate production in SM is stimulated. At the same time, the lipolysis is stimulated in AT, possibly to provide more energy to the muscle.

The stimulatory effect on muscle lactate by the norepinephrine infusion was transient. One possible explanation for this is catecholamine tachyphylaxis, i.e. desensitization of the adrenergic receptors in response to sustained catecholamine stimulation. Moreover, the circulating lactate concentrations increased to a lesser degree (15%) than in the SM (35%) during the norepinephrine infusion. At the same, plasma glucose was increased in a similar way. These findings might be associated with the Cori cycling of lactate and rapid hepatic lactate clearance for gluconeogenesis, although a direct effect of norepinephrine on hepatic glucose production cannot be disregarded. Furthermore, the lactate production in SM is considered to be higher in glycolytic type 2 fibers than in oxidative type 1 fibers and may consequently differ between various muscle groups (29). In the present study, only the gastrocnemius muscle was investigated, which has a predominant proportion of oxidative type 1 fibers (30).

To evaluate the effect of epinephrine, we investigated local tissue lactate release in response to insulin-induced hypoglycemia because hypoglycemia is the most powerful elicitor of endogenous epinephrine secretion (31). Because insulin stimulates fractional lactate release in AT but not in SM, these experiments were only performed in muscle (8). Indeed, in keeping with previous findings (8), the fractional SM lactate release remained unchanged during the initial part of the insulin infusion. On the other hand, in response to manifest hypoglycemia and increased epinephrine levels, it almost doubled and remained significantly elevated throughout the study period. Although the two experimental protocols with norepinephrine infusion and endogenous, hypoglycemia-induced epinephrine secretion cannot be directly compared, our findings indicate that epinephrine is a stronger stimulator of lactate production than norepinephrine in SM. Moreover, because epinephrine is a stronger β2-agonist than norepinephrine, these findings also suggested that the β-adrenergic regulation of SM lactate production mainly involves interaction with the β2-adrenoceptor. To explore further this notion, SM was perfused with selective β1–3-agonists in situ. In this substudy only the β2-agonist terbutaline caused a marked stimulation of muscle lactate. The β1-agonist dobutamine induced a minor but significant increase in interstitial lactate. Although functional β1-adrenoceptors have been identified in myocytes in experimental animals (32, 33), their role in human muscle tissue is a matter of debate. Thus, whether the dobutamine-induced increase in tissue lactate was a true physiological effect or the result of conformational changes of the β1-adrenoceptors and reduced agonist selectivity of dobutamine (34) is unclear. CGP-12177 was used as a β3-agonist because it has previously been shown that this drug has selective, albeit partial, β3-agonist activity in human adipocytes (35). Other compounds with varying β3-selectivity have been given to humans in vivo but have had negative side effects or necessitated very high dosages (36, 37). In this study, GCP-12177 did not affect the tissue lactate levels, which accords with previous reports that the β3-adrenoreceptor is absent in SM (38). Nevertheless, the β2-adrenoreceptor appears to be the most important receptor subtype in the β-adrenergic regulation of lactate production in SM. This is in keeping with the notion that the β2-receptor is the predominating β-adrenoreceptor subtype in SM in humans (39).

Note that interstitial lactate levels are also dependent on vascular effects. The influence of catecholamines on the local blood flow in AT and SM is a matter of uncertainty. Earlier studies have given divergent results with vasoconstriction, vasodilatation, or no vascular reaction being reported in SM and AT in response to catecholamine stimulation (27, 40, 41, 42, 43). In keeping with previous results, we registered a reduction of the muscle blood flow rates during norepinephrine stimulation (28). Therefore, we cannot exclude with certainty that the increase in interstitial lactate in response to norepinephrine was influenced by vasoconstriction and decreased lactate clearance. On the other hand, we found that augmentation of muscle lactate was combined with increased blood flow in response to the β2-agonist in situ, and with no changes in blood flow rates during the hypoglycemic clamp and endogenous epinephrine stimulation. Furthermore, there was no correlation between increases in muscle lactate levels and blood flow rates in the β2-agonist experiment. These findings strongly favor increased muscle tissue lactate production rather than blood flow effects. Therefore, the divergent direction of blood flow responses to the norepinephrine infusion and the in situ β2-agonist stimulation is best explained by {alpha}-adrenoreceptor-mediated vasoconstriction by norepinephrine in vivo because it is well established that the sympathetic nerve system mediates vasoconstriction through {alpha}-adrenoreceptor subtypes in the regulation of SM circulation (44, 45). Moreover, effects mediated by vascular {alpha}-adrenoreceptors could explain why tachyphylaxis was seen only by norepinephrine and not by epinephrine in vivo, and neither when the muscle was exposed to selective β-adrenoceptor agonists in situ.

In conclusion, our findings show that catecholamines stimulate lactate production in SM, but not in AT, and that the β2-adrenoreceptor seems to be the most important of the β-adrenergic receptor subtypes in the regulation of SM lactate production in humans.


   Footnotes
 
First Published Online November 6, 2007

Abbreviations: AT, Adipose tissue; SM, skeletal muscle.

Disclosure Statement: The authors have nothing to declare.

Received June 13, 2007.

Accepted October 26, 2007.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

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