Shriners Burns Hospital and the Departments of Surgery and Anesthesiology, The University of Texas Medical Branch, Galveston, Texas 77555
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ABSTRACT |
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The primary goal of this study was to investigate the effects of
glucose infusion on surfactant phosphatidylcholine (PC) metabolic
kinetics in the lungs. A new stable isotope tracer model was used
in which [1,2-13C2]acetate and
uniformly labeled [U-13C16]palmitate were
infused in 12 normal overnight-fasted pigs to quantify lung
surfactant kinetics with or without glucose infusion (24 mg · kg1 · min
1). With
glucose infusion, the rate of surfactant PC incorporation from de novo
synthesized palmitate increased from the control value of 2.1 ± 0.2 to 15.5 ± 1.9 nmol PC-bound
palmitate · h
1 · g wet
lung
1 (P < 0.05), whereas the
incorporation rate from plasma preformed palmitate decreased from the
control value of 20.9 ± 1.9 to 11.6 ± 1.1 nmol
palmitate · h
1 · g wet
lung
1 (P < 0.05). The palmitate
composition in lamellar body surfactant PC increased from the control
value of 61.7 ± 2.1% to 75.9 ± 0.6% (P < 0.05). The surfactant PC secretion rate decreased from the control
value of 239.0 ± 26.1 to 81.9 ± 5.3 nmol PC-bound
palmitate · h
1 · g wet
lung
1 (P < 0.05). We conclude that,
whereas surfactant secretion was inhibited by glucose infusion, neither
total surfactant PC synthesis nor the surfactant PC pool size was
significantly affected due to an increased reliance on de novo
synthesized fatty acids.
phosphatidylcholine; isotope; synthesis; secretion
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INTRODUCTION |
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ALTHOUGH THERE HAVE BEEN MANY in vitro investigations of the effects of glucose or insulin on surfactant production, the role of glucose and/or insulin on surfactant kinetics in vivo is still not clear. For example, Neufeld et al. (15) reported insulin inhibition of surfactant synthesis in fetal rabbit lung slices. Gross et al. (9) demonstrated a delay in the morphological maturation of the fetal rat lung in organ culture when insulin was present. On the other hand, Epstein et al. (7) found an increase in choline incorporation into phosphatidylcholine (PC) in lung slices from premature fetuses of glucose-intolerant monkeys. Wolfe et al. (20) found that insulin had a modest stimulatory effect on surfactant synthesis in the isolated perfused rat lung when palmitate concentrations were maintained constant. A direct in vivo assessment is needed to clarify the role of hyperglycemia/hyperinsulinemia on lung surfactant metabolism. This assessment is clinically important, because large amounts of glucose are commonly given as nutritional support to critically ill patients. Many of these patients have pulmonary complications, and any detrimental effect of glucose infusion on pulmonary surfactant would be reason to reevaluate the use of glucose as a primary caloric source.
The primary goal of this study was, therefore, to investigate the in
vivo effects of glucose infusion on surfactant kinetics. We have
recently developed a new isotope tracer methodology to quantify
surfactant kinetics in conscious pigs. This model enables, for the
first time, the quantification of surfactant PC synthesis from various
sources of fatty acids (FA), as well as the rates of surfactant
secretion, recycling, and irreversible loss. We have previously applied
this methodology to quantify surfactant PC metabolic kinetics in
conscious pigs in the normal postabsorptive state (14).
The same isotope tracer methodology, which involves 8 h of
constant infusions of [1,2-13C2]acetate
and [U-13C16]palmitate, was
applied in this study as in the previous study (14).
Physiological hyperglycemia, with attendant hyperinsulinemia, was
induced by the infusion of glucose at the rate of 24 mg · kg1 · min
1.
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METHODS |
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Tracer Infusion
Twelve Yorkshire swine (K-bar live stock, Sabinal, TX), were randomly divided into the control group (n = 6, weighing 16.4 ± 2.7 kg) and the glucose group (n = 6, weighing 15.3 ± 0.5 kg) in this study. All of the animals were given ketamine (20 mg/kg im; Ketaset, Fort Dodge Laboratories, Fort Dodge, IA) for surgical catheter placement. A venous catheter was inserted into the jugular vein for isotope tracer infusion, and a second catheter was inserted via the right common carotid artery into the abdominal aorta for blood sampling. After the surgical procedure, the animals were put into slings for later isotope infusion studies. When animals awakened from the surgery anesthesia (~1-1.5 h after completion of the surgical procedure), glucose infusion was started in the animals in the glucose group at the rate of 24 mg · kg
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BAL
The right lung was isolated, weighed, vacuum degassed, and suspended in a Plexiglas vacuum chamber via the trachea cannula, which passed through the top of the chamber to two 150-ml syringes connected by a three-way valve. A subatmospheric chamber pressure was externally applied to the lung, and the lung was filled with fluid consisting of normal saline plus 0.01 M Tris buffer through the syringes. This fluid was then withdrawn from the lung into the syringes by application of a positive pressure to the lung along with gentle airway suction. To ensure good mixing of BAL, the fluid collected in the syringes was pushed into the lung again and then withdrawn back into the syringes. The BAL was then transferred into a collecting flask. The entire procedure was repeated six times, so that six BAL washes were collected from each animal. The volume of each BAL wash was measured for the calculation of total PC content in BAL. Any fluid leaking from the lungs was collected and added to the appropriate BAL wash. The total alveolar PC pool size was calculated as the sum of the PC content from these six BAL washes.Sample Analysis
Alveolar surfactant isolation.
Lung surfactant from BAL was isolated according to a previously
described technique (4). The BAL was filtered through
gauze, and the volume was measured. An aliquot of BAL was centrifuged at 160 g for 20 min to remove intact cells and cellular
debris. The supernatant was collected and centrifuged in an
ultracentrifuge at 100,000 g for 1 h at 4°C (Model
XL-80 Beckman Ultracentrifuge, SW 40 TI rotor, Beckman Instruments,
Palo Alto, CA). The precipitate pellet was stored at 70°C for lipid extraction.
Lamellar body isolation.
After BAL collection, 0.5 g of lung tissue was minced and
homogenized in 1 M sucrose for 3 min (Brinkman Homogenizer, Brinkman Instrument, Westbury, NY). The homogenate was filtered, and the volume
was adjusted to 5 ml with 1 M sucrose. A discontinuous sucrose density
gradient from 0.9 to 0.2 M was loaded on top of the homogenates, as
described by Duck-Chong (6). The gradients were
centrifuged at 200 g for 15 min and then at 116,000 g for 3 h at 4°C. The lamellar bodies sedimented in
the 0.45 M sucrose layer were identified as a white opaque band similar
to that described by Duck-Chong and by Young et al. (23).
This band was aspirated, quantified by volume, and stored at 70°C
for lipid extraction.
PC isolation from surfactant. The lipids from the lamellar bodies and from BAL were extracted with a mixture of hydrochloric acid, heptane, and 2-propanol (1:10:40 by vol). The upper layer was aspirated and dried under nitrogen. The lipid extract was separated by thin-layer chromatography on a silica gel plate with a two-solvent system of 1) chloroform-methanol-water (65:30:5 by volume), and 2) heptane-ethyl ether-acetic glacial acid (80:20:2 by vol). The PC location was identified by iodine staining, scraped from the gel plate, and dissolved in 1 ml chloroform. A 250-µl aliquot was used for PC-bound palmitate enrichment measurements, a 250-µl aliquot was used for PC-bound FA composition determinations, and a 500-µl aliquot was used for phosphorus analysis according to the method described by Bartlett (5). [14C]dipalmitoyl PC was used to monitor the recovery (54 ± 2%) of this isolation procedure. The total PC contents in the lamellar bodies and BAL were used for calculation of surfactant PC synthetic rates and secretion rates, respectively.
FA isolation from plasma and PC from BAL and lamellar bodies.
Plasma (500 µl each) samples were extracted by use of a mixture of
hydrochloric acid, heptane, and 2-propanol (1:10:40 by vol). The upper
layer was collected and dried under nitrogen. The free fatty acid (FFA)
extract was isolated by thin-layer chromatography using a mixture of
heptane, glacial acetic acid, and ethyl ether (80:2:20 by vol). The
location of FFA was identified by iodine staining, scraped, and stored
at 70°C for the determination of isotope enrichment and composition.
FA enrichment measurement. The FA isolated from PC in BAL, lamellar bodies, and plasma were methylated with boron trifluoride in methanol, and the isotopic enrichment of palmitate methyl ester was determined by gas chromatography-mass spectrometry (GC-MS, model 5992, Hewlett-Packard) in the electron impact ionization mode. Ions of mass-to-charge ratio (m/z) 270(m + 0), 271(m + 1), 272(m + 2), 273(m + 3), 274(m + 4), and 286(m + 16) were selectively measured.
Concentration and composition. Plasma FFA composition and concentration from each hourly sampling were determined by HPLC (Waters 2690, Milford, MA), following the procedure described by Uji et al. (22). Heptadecanoic acid was used as an internal standard. FA compositions in lamellar body PC and alveolar surface PC from each animal were also measured by HPLC.
Plasma very low density lipoprotein-triglyceride isolation. Plasma very low density lipoprotein (VLDL) was isolated from 3 ml of plasma by overlaying the plasma with 0.9% normal saline with a density of 1.006 and subsequent ultracentrifugation at 50,000 rpm (171,500 g) for 20 h at 4°C. After ultracentrifugation, the VLDL was carefully removed along with the density solution by slicing the tube into sections (10). VLDL-triglyceride (VLDL-TG)-bound FA were isolated and measured following the same procedures as in PC-bound FA.
Blood glucose and plasma insulin concentrations were measured on hourly samples. Blood glucose was measured with a 2300 STAT analyzer (Yellow Spring Instruments, Yellow Springs, OH), and plasma insulin concentration was determined by a radioimmunoassay method (INCSTAR, Stillwater, MN).Calculation
The calculations of surfactant kinetics have been described in detail previously (14). Briefly, surfactant fractional synthetic rate was calculated as
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(1) |
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(2) |
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(3) |
The fractional synthetic rate (FSR) from de novo synthesized FA synthesized from places other than lung tissue was calculated as above, except for use of the TTR(m + 2) and TTR(m + 4) labels that came from plasma palmitate rather than from the lung tissue.
The absolute synthesis rate is calculated by multiplying the FSRsyn with the pool size of lamellar body PC-bound palmitate.
The fractional secretion rate is calculated as
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(4) |
We assume that a physiological steady state exists during the time of
measurements. In this case, the rate of irreversible loss of alveolar
surface PC must be equal to the sum of the synthetic rates from plasma
preformed palmitate and de novo synthesized palmitate. The recycling
rate is calculated by subtracting the secretion rate from the rate of
irreversible loss. Thus all the parameters represented in Fig.
2 can be quantified.
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Statistical Analysis
All results are expressed as means ± SE. Data from the control group have been published previously (14). To evaluate the effects of treatment on glucose and insulin concentrations, a two-way repeated-measures ANOVA was performed with the factors time and treatment. Post hoc comparisons at each time point were accomplished by use of Tukey's test. Other comparisons between the control and glucose groups were made with Student's t-test. Statistical significance is set at the 0.05 level. ![]() |
RESULTS |
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Blood Measurements
A physiological steady state was achieved in each pig during the 8-h isotope infusion, as indicated by the constant concentrations of plasma FFA, VLDL-TG, glucose, and insulin. The concentrations of blood glucose and plasma insulin in the control and glucose groups during the eight hourly isotope infusion are shown in Fig. 1, A and B, respectively. The average blood glucose level from the eight hourly samples was increased from the control value of 120 ± 9 to 148 ± 14 mg/dl (P < 0.05) during the glucose infusion. The average plasma insulin level from the eight hourly samples was also increased during the glucose infusion from the control value of 7.0 ± 0.6 to 17.9 ± 1.5 µIU/ml (P < 0.05).During the 8-h isotope infusion, arterial blood gas measurements in the
glucose group were: PaO2, 94 ± 4 Torr;
PaCO2, 41.3 ± 2.6 Torr; pH,
7.499 ± 0.030; and O2 content, 10.0 ± 0.4 vol%. There were no significant differences between the control and the glucose groups. With glucose infusion, the average of plasma total
fatty acid concentration from eight hourly samples taken during the 8-h
isotope infusion was decreased from the control value of 615 ± 73 to 104 ± 2 nmol/ml (P < 0.05). The average
plasma palmitate concentration was also decreased from the control
value of 183 ± 21 to 35 ± 1 nmol/ml (Table
1). However, the average proportionate
contribution of plasma palmitate to the total plasma FFA
increased from 29.7 ± 0.4% (control value) to 33.5 ± 0.3% (P < 0.05), whereas the contributions of plasma
oleate (18:1) were significantly decreased (Table 1).
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Pool Sizes and FA Composition of Surfactant
With glucose infusion, the surfactant PC pool size in the lamellar bodies was increased from the control value of 1.14 ± 0.02 to 1.41 ± 0.04 µmol/g wet lung (P < 0.05), and the PC pool size in the alveolar surface was decreased from the control value of 1.46 ± 0.12 to 1.09 ± 0.07 µmol/g wet lung (P < 0.05). The total surfactant PC pool sizes in lamellar bodies and alveolar surface remained the same. The proportionate contributions of palmitate to the lamellar body PC (75.9 ± 0.6% of FA) and in the alveolar surface PC (83.4 ± 0.8% of FA) were significantly increased compared with the control values of 61.7 ± 2.1 and 71.9 ± 1.4%, respectively (Table 2).
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Rates of Synthesis and Loss
Plasma palmitate enrichment [TTR(m + 16), Ep] reached an isotopic steady state (0.131 ± 0.011) within 2 h of [U-13C]palmitate infusion. At the end of the 8-h isotope infusion, the enrichments of TTR(m + 16) from lamellar PC-bound palmitate and alveolar surface PC-bound palmitate were 0.006 ± 0.000 and 0.002 ± 0.000, respectively. The enrichments of TTR(m + 2) and TTR(m + 4) from lamellar body PC-bound palmitate at the end of the infusion were 0.010 ± 0.001 and 0.013 ± 0.002, respectively. The calculated precursor enrichment (p) for palmitate that was de novo synthesized in lung tissue was 0.386 ± 0.036.With glucose infusion, the FSR of PC incorporation from de novo
synthesized palmitate in lung tissue was increased from the control
value of 0.14 ± 0.02 to 0.55 ± 0.07%/h (P < 0.05). At the same time, the FSR from plasma preformed palmitate was
decreased from the control value of 1.44 ± 0.13 to 0.54 ± 0.05%/h (P < 0.05). The synthetic rate from palmitate
that was de novo synthesized in lung tissue was increased from the
control value of 1.8 ± 0.2 to 12.0 ± 1.9 nmol PC-bound
palmitate · h1 · g wet
lung
1 (P < 0.05), and the synthetic rate
from palmitate that was de novo synthesized in other tissues was
increased from the control value of 0.3 ± 0.0 to 3.5 ± 0.3 nmol PC-bound palmitate · h
1 · g wet
lung
1 (P < 0.05). The synthetic rate
from plasma preformed palmitate was decreased from the control value of
20.9 ± 1.9 to 11.6 ± 1.1 nmol PC-bound
palmitate · h
1 · g wet
lung
1 (P < 0.05). However, the relative
synthetic rate from plasma preformed palmitate, which was calculated by
dividing the synthetic rate by plasma palmitate concentration, was
significantly increased from the control value of 0.111 ± 0.001 to 0.354 ± 0.021 ml · h
1 · g wet
lung
1 (P < 0.05).
Despite the significant changes in synthetic rates from de novo
synthesized palmitate and from plasma palmitate, the total synthetic
rates, which were equal to irreversible loss rates, were similar
between the control value (22.9 ± 2.1) and that with glucose
infusion (27.1 ± 2.4 nmol PC-bound
palmitate · h1 · g wet
lung
1).
Contribution of De Novo Synthesized FA of Different Origins to PC Synthesis
The FSR from de novo synthesized FA synthesized in lung tissue with glucose infusion was 0.55 ± 0.07%/h, whereas the FSR from FA synthesized elsewhere (other than in lung and liver) was 0.16 ± 0.02%/h. Therefore, lung tissue was the predominant site of de novo synthesized FA incorporated into surfactant PC.Rates of Secretion and Recycling
With glucose infusion, the calculated FSR (FSRsec) was decreased from the control value of 12.3 ± 2.0 to 4.5 ± 0.5%/h (P < 0.05). The secretion rate was decreased from the control value of 239.0 ± 26.1 to 81.9 ± 5.3 nmol PC-bound palmitate · h ![]() |
DISCUSSION |
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We recently developed a new tracer model to quantify surfactant PC kinetics in conscious animals (14). We found that, in the postabsorptive state, plasma was the primary source of FA used for surfactant PC synthesis (14). In the current study we found that 8 h of high-dose glucose infusion changed the proportional contribution of FA for surfactant PC synthesis, with de novo synthesized fatty acids playing a more predominant role. Because palmitate is the principal product of de novo synthesis, the percentage of palmitate in surfactant PC increased significantly during glucose infusion. A higher percentage of palmitate in surfactant PC should improve its surfactant function (21). Furthermore, although surfactant secretion and recycling were markedly decreased by glucose infusion, the rate of total surfactant synthesis was not affected. Consequently, despite significant changes in several aspects of surfactant kinetics, glucose did not affect the sum total of surfactant pools in the lamellar bodies and alveolar surface. Because the total surfactant pool size did not change and the change in the PC FA composition would likely be favorable with regard to function, we are unable to identify a role of hyperglycemia/hyperinsulinemia in causing pulmonary insufficiency via an effect on lung surfactant. To the contrary, our results indicate that, in clinical situations in which pulmonary function may be compromised, high-dose glucose ingestion may have a beneficial effect on pulmonary surfactant.
The decreased importance of plasma FA (specifically palmitate) as precursor for surfactant PC synthesis during glucose infusion can be attributed to the antilipolytic effect of insulin (12). Inhibition of lipolysis caused plasma FA to decrease to <20% of the control value. Nonetheless, plasma FFA remained the predominant source of FA for lung PC synthesis. This reflected a significant stimulation of the efficiency of synthesis of lung PC from plasma FFA as reflected by the significant increase in the rate of incorporation of plasma FFA when normalized for the prevailing plasma concentration. This finding is consistent with our previous study in the perfused rat lung (20), in which we found that the rate of incorporation of plasma palmitate into surfactant was stimulated by insulin when the palmitate concentration in the perfusate was maintained constant. Thus it appears that insulin does not exert a direct inhibitory effect on surfactant synthesis.
At the same time that plasma FA availability decreased, the incorporation of de novo fatty acids into pulmonary PC increased. Because palmitate is the product of de novo synthesis (8), the percentage of the contribution of palmitate to the newly synthesized surfactant PC also increased. The increased importance of de novo synthesized FA as precursors for PC synthesis likely reflects a stimulation of de novo synthesis by glucose. We previously found in normal human volunteers that the administration of a comparable amount of glucose for 24 h caused a significant increase in the synthesis of FA in the liver as well as total fat synthesis (1). Furthermore, in that study, we observed that the rates of fat synthesis increased severalfold more after 4 days of continuous high-dose glucose (1). It is thus likely that the increased incorporation of de novo synthesized FA into pulmonary surfactant PC observed in this study would have increased even further with more prolonged administration of glucose in the content of enteral or parenteral nutrition.
Our methodology enables the distinction of PC synthesis from plasma FFA that was preformed, as opposed to newly synthesized FA. Approximately 35% of the plasma FFA arose from de novo synthesis, a figure that may seem surprisingly high, because in human subjects, FA synthesis has been thought to occur mainly in the liver (3). However, in a recent study, we showed that, during high-dose glucose infusion in normal human volunteers, most de novo FA synthesis could not be explained by fatty acids synthesized in the liver and secreted as VLDL-TG (2). The accuracy of our estimation showing that a significant portion of the plasma FFA arose from de novo synthesis is supported by the significant increase in the proportionate contribution of palmitate to the total FFA (Table 2). Of course, the proportionate contribution of de novo synthesized FA to the plasma FFA was increased not only by the increased synthesis of palmitate but also by the suppression of lipolysis and subsequent release of preformed FFA into the blood from adipose tissue.
Whereas our methodology enables distinction between the incorporation
of plasma preformed FA and de novo synthesized FA into lung PC, the
methodology does not definitively identify all the sites of de novo
synthesized FA used for PC synthesis. However, we can distinguish
between de novo synthesis in the lung and in other tissues; we found
that the lung was the predominant site. The newly synthesized FA that
were produced elsewhere would have to be transported to the lungs via
the blood before incorporation into surfactant. We have discussed above
the quantitative contribution of de novo synthesized plasma FA. The
only other potentially significant source of circulating FA would be in
VLDL-TG; however, this source is not likely a major contribution to
lung PC FA. By measuring the secretion rates of VLDL-TG from de novo
synthesized FA in the current study as described previously
(1), we found that glucose increased the rate from
0.28 ± 0.06 to 7.34 ± 2.55 µmol VLDL-TG · kg1 · day
1. This
magnitude of increased VLDL-TG secretion of newly synthesized FA is
consistent with our previous results in humans (1) and indicates that hepatic FA synthesis can be markedly activated by
glucose infusion. The FA in circulating VLDL-TG are theoretically available to lung tissue. However, the rate of secretion of VLDL-TG is
not high in relation to lung PC synthesis. Thus the total delivery of
de novo synthesized palmitate to the lungs in the form of VLDL-TG was
4.32 µmol/h during glucose infusion. At the same time, de novo
synthesized palmitate was incorporated into pulmonary surfactant PC at
the rate of 3.0 µmol/h. Even if as much as 10% of VLDL-TG were
cleared by the lungs (which is a considerable overestimate of the
likely value) and all of the resulting palmitate were incorporated into
surfactant PC (again an unlikely exaggeration), the contribution of
this source of palmitate would still be only 14% of the total de novo
synthesized palmitate. Considering the liberal overestimates of both
VLDL-TG extraction and efficiency of incorporation into lung surfactant
PC used in this example, it is safe to conclude that circulating
VLDL-TG are not an important source of de novo synthesized FA for lung
surfactant PC. It is therefore reasonable to conclude that, during
glucose infusion, the lung is the major site of synthesis of de novo
synthesized palmitate that is subsequently incorporated into surfactant PC.
We assume that surfactant PC enrichment increases linearly and starts at the beginning of the 8-h isotope infusion (time 0). Our previous studies with different infusion time periods have shown a linear increase in surfactant PC enrichment (14). Although a delay in appearance of isotope label in surfactant PC might be expected, our previous data (14) have shown that this delay was insignificant compared with the 8-h infusion interval we used. Therefore, it is reasonable to assume that surfactant PC enrichment starts at time 0 and increases linearly.
The formula we used to calculate the fractional synthesis of lamellar
body PC assumes that there is no recycling of label from the alveolar
surface PC pool to the lamellar body PC pool. Our results show that
recycling rates of unlabeled alveolar PC to the lamellar body PC pool
are 2-10 times greater than the rates of synthesis of lamellar
body PC, which raises a concern for this assumption. However, because
the enrichment of the precursor for synthesis is much greater than the
enrichment of the alveolar surface PC over the 8-h infusion, the amount
of label in the lamellar body PC pool comes predominantly from
synthesis. Therefore, the effect of tracer recycling on PC synthesis is
not significant. We can express this effect of recycling on
FSRsyn in quantitative terms. In our previous study
(14), we demonstrated that, if the recycling does occur,
the formula to calculate the FSR is
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(5) |
Earlier papers (13, 16, and 18) have also concluded that palmitate in lung surfactant PC is derived from de novo synthesis within the lung. However, the important observation in the current study is that, when the relative pathways are quantified, it is only in the extremely lipogenic state of chronic high-dose glucose infusion that lung de novo synthesis plays an important role. Furthermore, even in this extreme circumstance of hyperglycemia/hyperinsulinemia, the contribution from plasma preformed palmitate was still similar to that from de novo synthesized palmitate in the lung (Fig. 2), even though the availability of FFA was low as a consequence of suppressed lipolysis. Furthermore, the persistent utilization of plasma FFA was striking when the relatively low proportion of palmitate in plasma FFA (~30%) is considered in light of the composition of lung surfactant PC (~70% palmitate). This reflects a high degree of selectivity in the synthesis process. Thus, although an increase in palmitate availability via the synthetic pathway resulted in a proportionate change in the relative amounts of individual FA in PC (i.e., increased proportion of palmitate), it is evident that precursor availability is of only limited importance in determining the composition of PC. Rather, it appears likely that composition is determined largely at the site of PC synthesis, presumably through a deacylation-reacylation pathway (17).
The findings of this paper are relevant to the clinical administration of high-dose glucose in the context of nutritional support. It is common in such patients that pulmonary problems, including decreased lung compliance, impair recovery. Past publications claiming an inhibitory effect of insulin on surfactant synthesis (9, 15) combined with increased CO2 production resulting from FA synthesis (19) have led to the general recommendation to limit glucose intake in critically ill patients. Our findings lend no support to this perspective. In fact, the increased proportion of palmitate in lung PC may even improve its surfactant function. On the other hand, we found that glucose infusion limited both secretion and recycling of surfactant PC. This occurred in the absence of any change in the total surfactant pool size, so it is unclear whether there is a physiological consequence of decreased secretion/recycling. Thus, whereas in the absence of any compelling evidence to the contrary it is reasonable to conclude that nutritional support with glucose/carbohydrate presents no detriment to surfactant function, further evidence regarding the physiological significance of altered secretion/recycling over a prolonged period of time may cause a revision of this conclusion. With regard to respiratory distress in infants of diabetic mothers, our results indicate that it is unlikely that insulin per se or hyperglycemia directly limits surfactant synthesis.
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ACKNOWLEDGEMENTS |
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We thank Lillian Traber and colleagues for their guidance in performing this study.
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FOOTNOTES |
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This investigation was supported by National Institutes of Health Grant 2R01 DK-34817-15 and Shriners Hospital Grants 8050 and 8490.
Address for reprint requests and other correspondence: R. R. Wolfe, Shriners Burns Hospital, 815 Market St., Galveston, TX 77550 (E-mail: rwolfe{at}sbi.utmb.edu).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 24 January 2000; accepted in final form 16 May 2000.
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