Effect of polyamines and cystic fibrosis serum on glucose transport.

The effect of plasma or serum from homozygotes and heterozygotes for the 
cystic fibrosis (CF) gene on the active uptake of 3-0-14C-methyl- D-glucose 
(3-0-14C-MDG) by rat jejunal epithelium was studied. Furthermore, the role of 
the polyamine, spermidine, and its products of metabolic degradation on glucose 
transport were investigated, and a relationship to the pathogenesis of membrane 
dysfunction in cystic fibrosis was postulated. Glucose transport in everted rat 
jejunal rings was used in the study. Results were expressed as 
3-0-14C-MDG concentration ratio between the intracellular (ICF) and the extracellular fluid 
spaces (ECF) of the jejunal rings at the end of a 
60 min incubation period. The mean ratio obtained from incubations of 
the rat jejunal rings in medium consisting of Krebs-Ringer- bicarbonate buffer 
and the labeled sugar was considered as 100% uptake. When plasma 
or serum, with or without spermidine, was mixed with the medium 
in a volume ratio of 1:3, a decrease in the active 
uptake of 3-0-14C-MDG was observed, expressed as percent inhibition. Percent inhibition 
of 3-0-14C-MDG uptake obtained when the rat jejunal rings were incubated 
in normal plasma was compared to that obtained with plasma from 
cystic fibrosis genotypes. It was found that: 1) plasma from 25 
homozygous children had greater inhibitory effect on glucose uptake than plasma 
from 26 normal children; 2) plasma from 9 heterozygous women had 
greater inhibitory effect than that from 6 normal women; 3) the 
inhibitory effect of plasma from 3 homozygous children was not influenced 
by dialysis; 4) the inhibitory effects of paired plasma and serum 
samples from 9 homozygotes were comparable; 5) spermidine added to the 
incubating electrolyte solution did not affect glucose transport; 6) the addition 
of spermidine to reaction mixtures containing normal plasma potentiated the inhibitory 
effect; and 7) mixing and incubation of fresh bovine serum with 
reaction mixtures containing plasma from homozygotes decreased the inhibitory effect. The 
predominant inhibitory effect of plasma or serum from homozygotes and heterozygotes 
for the CF gene appears to be related to a nondialyzeable 
molecule(s). It does not seem to reflect the presence of high 
plasma glucose levels in cystic fibrosis nor to be the result 
of competitive inhibition between sugars. It does not seem to be 
the result of sodium or other electrolyte differences. A similar inhibitory 
effect is acquired by normal plasma after the addition of spermidine. 
On the other hand, plasma from CF homozygotes loses its inhibitory 
effect after incubation with fresh bovine serum. These findings may indicate 
that products of metabolic degradation of spermidine are responsible for the 
inhibitory effect of glucose transport and suggest the possibility of a 
role in abnormal polyamine metabolism in the pathogenesis of cystic fibrosis. 
