Glucose effects on lung surfactant kinetics in conscious pigs

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 · kg−1 · 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.

Download Full-text

Lung surfactant kinetics in conscious pigs

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1999.277.1.e187 ◽

1999 ◽

Vol 277 (1) ◽

pp. E187-E195 ◽

Cited By ~ 5

Author(s):

Wenjun Z. Martini ◽

David L. Chinkes ◽

Robert E. Barrow ◽

E. D. Murphey ◽

Robert R. Wolfe

Keyword(s):

Fatty Acids ◽

Low Dose ◽

De Novo ◽

Lung Surfactant ◽

Lamellar Body ◽

Lamellar Bodies ◽

Stable Isotope Tracer ◽

Isotope Tracer ◽

Effect Of Glucose ◽

Alveolar Surface

The primary goal of this study was to determine the contributions of plasma free fatty acids (FFA) and de novo synthesized fatty acids (FA) to lung surfactant phosphatidylcholine (PC) synthesis. A new stable isotope tracer model was developed in which [1,2-13C2]acetate and uniformly labeled [U-13C16]palmitate were infused in nine normal overnight fasted pigs to quantify surfactant kinetics in the basal state and during low-dose glucose infusion (2 mg ⋅ kg−1 ⋅ min−1). There was no effect of glucose; therefore, all data were pooled. The surfactant PC-bound palmitate incorporation rate from plasma palmitate was 20.9 ± 1.9 nmol palmitate ⋅ h−1 ⋅ g wet lung−1, compared with the rate of 2.1 ± 0.3 nmol palmitate ⋅ h−1 ⋅ g wet lung−1 from de novo synthesized palmitate. The PC-bound palmitate secretion rate from the lamellar body pool to the alveolar surface pool was 239 ± 26 nmol palmitate ⋅ h−1 ⋅ g wet lung−1. Approximately 90% of the secreted PC recycled back to the lamellar bodies for reutilization. We conclude that plasma is the primary contributor of FA for surfactant PC synthesis under the conditions of this experiment.

Download Full-text

Regulation of lung surfactant secretion

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1990.258.6.l241 ◽

1990 ◽

Vol 258 (6) ◽

pp. L241-L253 ◽

Cited By ~ 34

Author(s):

A. Chander ◽

A. B. Fisher

Keyword(s):

Lung Surfactant ◽

Protein A ◽

Lamellar Body ◽

Surfactant Protein ◽

Ventilation Rate ◽

Future Research ◽

Surfactant Secretion ◽

Vasopressin Receptors ◽

Protein Components

Secretion of lung surfactant is the direct step in release of the lipoprotein-like product, synthesized in lung epithelial type II cells, onto the alveolar surface. Release of surfactant phosphatidylcholine (PC) proceeds via formation of surface pores during exocytosis of lamellar bodies. Surfactant secretion is regulated locally in the lung by changes in ventilation rate, possibly mediated by distension and altered intracellular pH. Secretion is also stimulated by various agents, including agonists for beta-adrenergic, purinoceptors, and vasopressin receptors and is associated with increased cytosolic Ca2+, cellular adenosine 3',5'-cyclic monophosphate, and activation of protein kinases. Limited studies suggest that secretion of surfactant protein A may be regulated by both cAMP-dependent and protein kinase C-dependent pathways. The integration of these various mechanisms for the in vivo regulation of surfactant secretion remains largely unexplored. Future research into the mechanisms involved in lamellar body fusion with the plasma membrane, role of protein phosphorylation, transient changes in cAMP and Ca2+, and coordination between the secretion of phospholipid and protein components of surfactant should enhance our understanding of secretion of surfactant “lipoprotein.”

Download Full-text

Faculty Opinions recommendation of Lung surfactant secretion by interalveolar Ca2+ signaling.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1003697.374609 ◽

2006 ◽

Author(s):

Machiko Ikegami

Keyword(s):

Lung Surfactant ◽

Surfactant Secretion

Download Full-text

Species pattern of phosphatidylinositol from lung surfactant and a comparison of the species pattern of phosphatidylinositol and phosphatidylglycerol synthesized de novo in lung microsomal fractions

Biochemical Journal ◽

10.1042/bj2540067 ◽

1988 ◽

Vol 254 (1) ◽

pp. 67-71 ◽

Cited By ~ 9

Author(s):

B Rüstow ◽

Y Nakagawa ◽

H Rabe ◽

K Waku ◽

D Kunze

Keyword(s):

Lung Function ◽

Molecular Species ◽

De Novo ◽

Lung Surfactant ◽

Minor Component ◽

Main Species ◽

Surfactant Phospholipids ◽

Species Pattern ◽

A Minor

1. Phosphatidylinositol (PI) is a minor component of lung surfactant which may be able to replace the functionally important phosphatidylglycerol (PG) [Beppu, Clements & Goerke (1983) J. Appl. Physiol. 55, 496-502] without disturbing lung function. The dipalmitoyl species is one of the main species for both PI (14.4%) and PG (16.9%). Besides the C16:0--C16:0 species, the C16:0--C18:0, C16:0--C18:1, C16:0--C18:2 and C18:0--C18:1 species showed comparable proportions in the PG and PI fractions. These similarities of the species patterns and the acidic character of both phospholipids could explain why surfactant PG may be replaced by PI. 2. PI and PG were radiolabelled by incubation of microsomal fractions with [14C]glycerol 3-phosphate (Gro3P). For 11 out of 14 molecular species of PI and PG we measured comparable proportions of radioactivity. The radioactivity of these 11 species accounted together for more than 80% of the total. The addition of inositol to the incubation system decreased the incorporation in vitro of Gro3P into PG and CDP-DG (diacylglycerol) of lung microsomes (microsomal fractions), but did not change the distribution of radioactivity among the molecular species of PG. These results supported the idea that both acidic surfactant phospholipids may be synthesized de novo from a common CDP-DG pool in lung microsomes.

Download Full-text