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Use of fetal streptozotocin injection to determine the role of normal levels of fetal insulin in regulating uteroplacental and umbilical glucose exchange.

Abstract

The present study was performed to determine the role of the normal fetal concentration of insulin in regulating placental-fetal glucose exchange. Fetal insulin deficiency was produced by streptozotocin injection into near term fetal sheep, and the effects of this insulin deficiency on net uteroplacental glucose uptake and net umbilical glucose uptake were measured. Each fetus received two or three doses of streptozotocin, 100 mg.kg-1.dose-1, given on separate days. This dosage of streptozotocin produced a 97.6% reduction in fetal pancreatic insulin content, a fall in fetal plasma insulin concentration (21 +/- 2 to 10 +/- 1 microU.ml-1), a rise in fetal plasma glucagon concentration (57 +/- 4 to 114 +/- 19 pg.ml-1), a rise in fetal blood glucose concentration (20.4 +/- 0.9 to 33.4 +/- 4.4 mg.dl-1), and a failure of insulin secretion in response to glucose infusion. Fetal blood oxygen content and umbilical oxygen uptake were normal and did not change during the entire study. Umbilical glucose uptake was reduced by 66% (5.98 +/- 0.38 to 2.02 +/- 1.31 mg.min-1.kg-1) after the streptozotocin-induced hypoinsulinemia and hyperglycemia but was returned to the control level by an insulin infusion into the fetus that reestablished the control maternal to fetal glucose concentration gradient. Net uteroplacental glucose uptake (consumption) did not change throughout the study. Because glucose concentration and umbilical glucose uptake could be normalized by an insulin infusion, it is unlikely that direct or toxic effects of streptozotocin on fetal or placental glucose metabolism were primarily responsible for the hyperglycemia and the reduced rate of umbilical glucose uptake.(

ABSTRACT

TRUNCATED AT 250 WORDS)

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  • Authors+Show Affiliations

    ,

    Department of Pediatric, University of Colorado School of Medicine, Denver 80262.

    Source

    Pediatric research 24:3 1988 Sep pg 312-7

    MeSH

    Animals
    Blood Glucose
    Female
    Fetal Blood
    Glucose
    Insulin
    Maternal-Fetal Exchange
    Oxygen
    Oxygen Consumption
    Placenta
    Pregnancy
    Reference Values
    Sheep
    Streptozocin
    Umbilical Cord
    Uterus

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

    Language

    eng

    PubMed ID

    2974939

    Citation

    Hay, W W., and H K. Meznarich. "Use of Fetal Streptozotocin Injection to Determine the Role of Normal Levels of Fetal Insulin in Regulating Uteroplacental and Umbilical Glucose Exchange." Pediatric Research, vol. 24, no. 3, 1988, pp. 312-7.
    Hay WW, Meznarich HK. Use of fetal streptozotocin injection to determine the role of normal levels of fetal insulin in regulating uteroplacental and umbilical glucose exchange. Pediatr Res. 1988;24(3):312-7.
    Hay, W. W., & Meznarich, H. K. (1988). Use of fetal streptozotocin injection to determine the role of normal levels of fetal insulin in regulating uteroplacental and umbilical glucose exchange. Pediatric Research, 24(3), pp. 312-7.
    Hay WW, Meznarich HK. Use of Fetal Streptozotocin Injection to Determine the Role of Normal Levels of Fetal Insulin in Regulating Uteroplacental and Umbilical Glucose Exchange. Pediatr Res. 1988;24(3):312-7. PubMed PMID: 2974939.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Use of fetal streptozotocin injection to determine the role of normal levels of fetal insulin in regulating uteroplacental and umbilical glucose exchange. AU - Hay,W W,Jr AU - Meznarich,H K, PY - 1988/9/1/pubmed PY - 2001/3/28/medline PY - 1988/9/1/entrez SP - 312 EP - 7 JF - Pediatric research JO - Pediatr. Res. VL - 24 IS - 3 N2 - The present study was performed to determine the role of the normal fetal concentration of insulin in regulating placental-fetal glucose exchange. Fetal insulin deficiency was produced by streptozotocin injection into near term fetal sheep, and the effects of this insulin deficiency on net uteroplacental glucose uptake and net umbilical glucose uptake were measured. Each fetus received two or three doses of streptozotocin, 100 mg.kg-1.dose-1, given on separate days. This dosage of streptozotocin produced a 97.6% reduction in fetal pancreatic insulin content, a fall in fetal plasma insulin concentration (21 +/- 2 to 10 +/- 1 microU.ml-1), a rise in fetal plasma glucagon concentration (57 +/- 4 to 114 +/- 19 pg.ml-1), a rise in fetal blood glucose concentration (20.4 +/- 0.9 to 33.4 +/- 4.4 mg.dl-1), and a failure of insulin secretion in response to glucose infusion. Fetal blood oxygen content and umbilical oxygen uptake were normal and did not change during the entire study. Umbilical glucose uptake was reduced by 66% (5.98 +/- 0.38 to 2.02 +/- 1.31 mg.min-1.kg-1) after the streptozotocin-induced hypoinsulinemia and hyperglycemia but was returned to the control level by an insulin infusion into the fetus that reestablished the control maternal to fetal glucose concentration gradient. Net uteroplacental glucose uptake (consumption) did not change throughout the study. Because glucose concentration and umbilical glucose uptake could be normalized by an insulin infusion, it is unlikely that direct or toxic effects of streptozotocin on fetal or placental glucose metabolism were primarily responsible for the hyperglycemia and the reduced rate of umbilical glucose uptake.(ABSTRACT TRUNCATED AT 250 WORDS) SN - 0031-3998 UR - https://www.unboundmedicine.com/medline/citation/2974939/Use_of_fetal_streptozotocin_injection_to_determine_the_role_of_normal_levels_of_fetal_insulin_in_regulating_uteroplacental_and_umbilical_glucose_exchange_ L2 - http://dx.doi.org/10.1203/00006450-198809000-00007 DB - PRIME DP - Unbound Medicine ER -