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Original Articles

Uptake of myo-Inositol by Early-Somite Rat Conceptus: Transport Kinetics and Effects of Hyperglycemia

  1. Marc J Weigensberg,
  2. Francisco-José Garcia-Palmer and
  3. Norbert Freinkel
  1. center for Endocrinology Metabolism, and Nutrition Department of Medicine; Department of Molecular Biology; and the World Health Organization Collaborating Center for Diabetes in Pregnancy, Northwestern University Medical School Chicago, Illinois
  1. Address correspondence and reprint requests to Marc J. Weigensberg, MD, Cook County Children's Hospital, 700 South Wood Street, Room 121, Chicago, IL 60612.
Diabetes 1990 May; 39(5): 575-582. https://doi.org/10.2337/diab.39.5.575
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Abstract

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 μM) 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. Thus, our findings indicate that the concentrative uptake of myo-inositol by the early postimplantation rat conceptus occurs via a comparatively slow transport that may be Na+ dependent and is competitively affected by extracellular glucose. We suggest that the impairment of free myo-inositol uptake and retention by high glucose and the attendant diminution in the incorporation of the myo-inositol into phosphoinositides may contribute to the embryopathic potential of hyperglycemia.

  • Received October 7, 1989.
  • Revision received January 11, 1990.
  • Accepted January 11, 1990.
  • Copyright © 1990 by the American Diabetes Association

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May 1990, 39(5)
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Uptake of myo-Inositol by Early-Somite Rat Conceptus: Transport Kinetics and Effects of Hyperglycemia
Marc J Weigensberg, Francisco-José Garcia-Palmer, Norbert Freinkel
Diabetes May 1990, 39 (5) 575-582; DOI: 10.2337/diab.39.5.575

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Uptake of myo-Inositol by Early-Somite Rat Conceptus: Transport Kinetics and Effects of Hyperglycemia
Marc J Weigensberg, Francisco-José Garcia-Palmer, Norbert Freinkel
Diabetes May 1990, 39 (5) 575-582; DOI: 10.2337/diab.39.5.575
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