Uptake of myo-inositol by early-somite rat conceptus. Transport kinetics and effects of hyperglycemia.
We have shown that myo-inositol in the cultured rat embryo is diminished whenever malformations are induced by hyperglycemia and that the malformations and reductions of tissue myo-inositol content are not corrected by aldose reductase inhibitors. This study was designed to evaluate the kinetics of myo-[3H]inositol uptake in vitro during 1-, 3-, and 24-h intervals in the 10.5-day rat conceptus (10-12 somites). We found that the equilibration between tissue and medium is relatively slow and that the concentration of free myo-inositol in tissue is only approximately threefold greater than in the medium even after 24 h. The integrated uptake of free myo-inositol by the intact 10.5-day conceptus is a saturable process with a Km (246 +/- 16 microM) consistent with a low-affinity system. The net rate of accumulation into the tissue pool of free myo-inositol exceeds the rate of incorporation of the accumulated myo-inositol into lipid components. Ambient glucose inhibits net myo-inositol uptake in a concentration-dependent fashion, and the inhibition is competitive in nature. The glucose-mediated inhibitions of myo-inositol transport also compromise the concurrent incorporation of myo-[3H]inositol into lipid components, although to a lesser extent. These inhibitory effects are relatively specific for D-glucose and not replicated by equimolar additions of D-mannose or D-galactose. myo-Inositol accumulation by the 10.5-day rat conceptus is also impaired by relatively specific inhibitors of D-glucose transport such as phloridzin or ouabain.(ABSTRACT TRUNCATED AT 250 WORDS)
Weigensberg
M J
MJ
Center for Endocrinology, Metabolism and Nutrition, Northwestern University Medical School, Chicago, Illinois.
Garcia-Palmer
F J
FJ
Freinkel
N
N
D000818:Animals; D001692:Biological Transport; D000013:Congenital Abnormalities / Q000209:etiology; D046508:Culture Techniques; D004247:DNA / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006601:Hexoses / Q000494:pharmacology; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D007294:Inositol / Q000378:metabolism*; D007700:Kinetics; D050356:Lipid Metabolism; D011247:Pregnancy; D011506:Proteins / Q000378:metabolism
D006601:Hexoses; D011506:Proteins; D007294:Inositol; D004247:DNA; D005947:Glucose