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Glucose-stimulated insulin response in pregnant sheep following acute suppression of plasma non-esterified fatty acid concentrations.

Abstract

BACKGROUND

Elevated non-esterified fatty acids (NEFA) concentrations in non-pregnant animals have been reported to decrease pancreatic responsiveness. As ovine gestation advances, maternal insulin concentrations fall and NEFA concentrations increase. Experiments were designed to examine if the pregnancy-associated rise in NEFA concentration is associated with a reduced pancreatic sensitivity to glucose in vivo. We investigated the possible relationship of NEFA concentrations in regulating maternal insulin concentrations during ovine pregnancy at three physiological states, non-pregnant, non-lactating (NPNL), 105 and 135 days gestational age (dGA, term 147+/- 3 days).

METHODS

The plasma concentrations of insulin, growth hormone (GH) and ovine placental lactogen (oPL) were determined by double antibody radioimmunoassay. Insulin responsiveness to glucose was measured using bolus injection and hyperglycaemic clamp techniques in 15 non-pregnant, non-lactating ewes and in nine pregnant ewes at 105 dGA and near term at 135 dGA. Plasma samples were also collected for hormone determination. In addition to bolus injection glucose and insulin Area Under Curve calculations, the Mean Plasma Glucose Increment, Glucose Infusion Rate and Mean Plasma Insulin Increment and Area Under Curve were determined for the hyperglycaemic clamp procedures. Statistical analysis of data was conducted with Students t-tests, repeated measures ANOVA and 2-way ANOVA.

RESULTS

Maternal growth hormone, placental lactogen and NEFA concentrations increased, while basal glucose and insulin concentrations declined with advancing gestation. At 135 dGA following bolus glucose injections, peak insulin concentrations and insulin area under curve (AUC) profiles were significantly reduced in pregnant ewes compared with NPNL control ewes (p < 0.001 and P < 0.001, respectively). In hyperglycaemic clamp studies, while maintaining glucose levels not different from NPNL ewes, pregnant ewes displayed significantly reduced insulin responses and a maintained depressed insulin secretion. In NPNL ewes, 105 and 135 dGA ewes, the Glucose Infusion Rate (GIR) was constant at approximately 5.8 mg glucose/kg/min during the last 40 minutes of the hyperglycaemic clamp and the Mean Plasma Insulin Increment (MPII) was only significantly (p < 0.001) greater in NPNL ewes. Following the clamp, NEFA concentrations were reduced by approximately 60% of pre-clamp levels in all groups, though a blunted and suppressed insulin response was maintained in 105 and 135 dGA ewes.

CONCLUSIONS

Results suggest that despite an acute suppression of circulating NEFA concentrations during pregnancy, the associated steroids and hormones of pregnancy and possibly NEFA metabolism, may act to maintain a reduced insulin output, thereby sparing glucose for non-insulin dependent placental uptake and ultimately, fetal requirements.

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  • Authors+Show Affiliations

    ,

    Commonwealth Scientific and Industrial Research Organization, Division of Animal Production, Prospect, NSW Australia. Tim.regnault@uchsc.edu

    , , ,

    Source

    MeSH

    Animals
    Blood Glucose
    Body Weight
    Fatty Acids, Nonesterified
    Female
    Gestational Age
    Glucose
    Glucose Clamp Technique
    Growth Hormone
    Hyperglycemia
    Infusions, Intravenous
    Insulin
    Lactation
    Placental Lactogen
    Pregnancy
    Sheep, Domestic

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    15352999

    Citation

    Regnault, Timothy R H., et al. "Glucose-stimulated Insulin Response in Pregnant Sheep Following Acute Suppression of Plasma Non-esterified Fatty Acid Concentrations." Reproductive Biology and Endocrinology : RB&E, vol. 2, 2004, p. 64.
    Regnault TR, Oddy HV, Nancarrow C, et al. Glucose-stimulated insulin response in pregnant sheep following acute suppression of plasma non-esterified fatty acid concentrations. Reprod Biol Endocrinol. 2004;2:64.
    Regnault, T. R., Oddy, H. V., Nancarrow, C., Sriskandarajah, N., & Scaramuzzi, R. J. (2004). Glucose-stimulated insulin response in pregnant sheep following acute suppression of plasma non-esterified fatty acid concentrations. Reproductive Biology and Endocrinology : RB&E, 2, p. 64.
    Regnault TR, et al. Glucose-stimulated Insulin Response in Pregnant Sheep Following Acute Suppression of Plasma Non-esterified Fatty Acid Concentrations. Reprod Biol Endocrinol. 2004 Sep 7;2:64. PubMed PMID: 15352999.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Glucose-stimulated insulin response in pregnant sheep following acute suppression of plasma non-esterified fatty acid concentrations. AU - Regnault,Timothy R H, AU - Oddy,Hutton V, AU - Nancarrow,Colin, AU - Sriskandarajah,Nadarajah, AU - Scaramuzzi,Rex J, Y1 - 2004/09/07/ PY - 2004/06/27/received PY - 2004/09/07/accepted PY - 2004/9/9/pubmed PY - 2005/7/28/medline PY - 2004/9/9/entrez SP - 64 EP - 64 JF - Reproductive biology and endocrinology : RB&E JO - Reprod. Biol. Endocrinol. VL - 2 N2 - BACKGROUND: Elevated non-esterified fatty acids (NEFA) concentrations in non-pregnant animals have been reported to decrease pancreatic responsiveness. As ovine gestation advances, maternal insulin concentrations fall and NEFA concentrations increase. Experiments were designed to examine if the pregnancy-associated rise in NEFA concentration is associated with a reduced pancreatic sensitivity to glucose in vivo. We investigated the possible relationship of NEFA concentrations in regulating maternal insulin concentrations during ovine pregnancy at three physiological states, non-pregnant, non-lactating (NPNL), 105 and 135 days gestational age (dGA, term 147+/- 3 days). METHODS: The plasma concentrations of insulin, growth hormone (GH) and ovine placental lactogen (oPL) were determined by double antibody radioimmunoassay. Insulin responsiveness to glucose was measured using bolus injection and hyperglycaemic clamp techniques in 15 non-pregnant, non-lactating ewes and in nine pregnant ewes at 105 dGA and near term at 135 dGA. Plasma samples were also collected for hormone determination. In addition to bolus injection glucose and insulin Area Under Curve calculations, the Mean Plasma Glucose Increment, Glucose Infusion Rate and Mean Plasma Insulin Increment and Area Under Curve were determined for the hyperglycaemic clamp procedures. Statistical analysis of data was conducted with Students t-tests, repeated measures ANOVA and 2-way ANOVA. RESULTS: Maternal growth hormone, placental lactogen and NEFA concentrations increased, while basal glucose and insulin concentrations declined with advancing gestation. At 135 dGA following bolus glucose injections, peak insulin concentrations and insulin area under curve (AUC) profiles were significantly reduced in pregnant ewes compared with NPNL control ewes (p < 0.001 and P < 0.001, respectively). In hyperglycaemic clamp studies, while maintaining glucose levels not different from NPNL ewes, pregnant ewes displayed significantly reduced insulin responses and a maintained depressed insulin secretion. In NPNL ewes, 105 and 135 dGA ewes, the Glucose Infusion Rate (GIR) was constant at approximately 5.8 mg glucose/kg/min during the last 40 minutes of the hyperglycaemic clamp and the Mean Plasma Insulin Increment (MPII) was only significantly (p < 0.001) greater in NPNL ewes. Following the clamp, NEFA concentrations were reduced by approximately 60% of pre-clamp levels in all groups, though a blunted and suppressed insulin response was maintained in 105 and 135 dGA ewes. CONCLUSIONS: Results suggest that despite an acute suppression of circulating NEFA concentrations during pregnancy, the associated steroids and hormones of pregnancy and possibly NEFA metabolism, may act to maintain a reduced insulin output, thereby sparing glucose for non-insulin dependent placental uptake and ultimately, fetal requirements. SN - 1477-7827 UR - https://www.unboundmedicine.com/medline/citation/15352999/Glucose_stimulated_insulin_response_in_pregnant_sheep_following_acute_suppression_of_plasma_non_esterified_fatty_acid_concentrations_ L2 - https://rbej.biomedcentral.com/articles/10.1186/1477-7827-2-64 DB - PRIME DP - Unbound Medicine ER -