Ih. Gewolb et J. Obrien, SURFACTANT SECRETION BY TYPE-II PNEUMOCYTES IS INHIBITED BY HIGH GLUCOSE-CONCENTRATIONS, Experimental lung research, 23(3), 1997, pp. 245-255
Delayed fetal lung maturation is observed in poorly controlled diabeti
c pregnancies. To investigate whether elevated glucose levels inhibit
basal surfactant secretion and synthesis in type II cells and whether
inhibitory effects on secretion can be reversed by secretagogues, type
II cells isolated from 20-day fetal rat lung explants were initially
cultured in [H-3] choline containing media with glucose concentrations
of 5.5, 10, 25, 50, and 100 mM, or in equiosmolar mannitol controls.
Further incubation in nonradioactive media containing matched glucose
levels with and without 1 x 10(-5) M terbutaline or 1 x 10(-6) M and 1
x 10(-8) M 12-O-tetradecanoylphorbol 13-acetate (TPA) allowed assessm
ent of incorporation of choline into phosphatidylcholine (PC) and its
subsequent secretion. PC secretion was inhibited by culture in high gl
ucose conditions, resulting in an similar to 30% ro reduction in secre
tion under 50 and 100 mM glucose conditions compared to culture at 5.5
or 10 mM glucose (p <.01); this decrease could not be explained by ch
anges in osmolarity or in cell viability after culture in high glucose
. Insulin (I unit/mL) had no significant impact on secretion (92 +/- 7
% of control). Terbutaline-stimulated cells grown under 50 and 100 mM
glucose conditions had significantly lower secretion rates than did te
rbutaline-stimulated cells cultured in 5.5 mM glucose (p <.05). Exposu
re to TPA resulted in significant increases in surfactant secretion by
cells grown in both 5.5 and 100 mM glucose; however, the percentage i
ncrease (39.5 +/- 6.8% and 94.8 +/- 8.0% with 10(-8) M and 10(-6) M TP
A, respectively) was significantly lower than in controls (87.8 +/- 8.
0% and 152.1 +/- 18.8%, respectively) (p <.001). Choline incorporation
into PC was also decreased by 100 mM glucose to 77 +/- 9% of control
(p <.01). These data indicate that high glucose levels inhibit both su
rfactant synthesis and baseline and secretagogue-stimulated surfactant
secretion by type II cells. This inhibitory effect on surfactant secr
etion may further exacerbate the decrease in surfactant synthesis and
the pulmonary maturational delay seen in infants of diabetic pregnanci
es.