Adaptation of ovine fetal pancreatic insulin secretion to chronic hypoglycaemia and euglycaemic correction

Limesand, Sean W.; Hay, William W.

doi:10.1111/j.1469-7793.2003.00095.x

Cited by 31 publications

(40 citation statements)

References 54 publications

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“…This may be related to decreased fetal glucose uptake from the placenta, which we demonstrated previously following chronic fetal amino acid infusions (30). Lower fetal glucose concentrations lead to decreased fetal insulin secretion (28). Fetal arterial plasma cortisol and norepinephrine were nearly doubled in the AA group, although these failed to reach statistical significance.…”

Section: Discussionmentioning

confidence: 85%

Increased amino acid supply potentiates glucose-stimulated insulin secretion but does not increase β-cell mass in fetal sheep

Gadhia

Maliszewski

O'Meara

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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Amino acids and glucose acutely stimulate fetal insulin secretion. In isolated adult pancreatic islets, amino acids potentiate glucose-stimulated insulin secretion (GSIS), but whether amino acids have this same effect in the fetus is unknown. Therefore, we tested the effects of increased fetal amino acid supply on GSIS and morphology of the pancreas. We hypothesized that increasing fetal amino acid supply would potentiate GSIS. Singleton fetal sheep received a direct intravenous infusion of an amino acid mixture (AA) or saline (CON) for 10-14 days during late gestation to target a 25-50% increase in fetal branched-chain amino acids (BCAA). Early-phase GSIS increased 150% in the AA group (P < 0.01), and this difference was sustained for the duration of the hyperglycemic clamp (105 min) (P < 0.05). Glucose-potentiated arginine-stimulated insulin secretion (ASIS), pancreatic insulin content, and pancreatic glucagon content were similar between groups. β-Cell mass and area were unchanged between groups. Baseline and arginine-stimulated glucagon concentrations were increased in the AA group (P < 0.05). Pancreatic α-cell mass and area were unchanged. Fetal and pancreatic weights were similar. We conclude that a sustained increase of amino acid supply to the normally growing late-gestation fetus potentiated fetal GSIS but did not affect the morphology or insulin content of the pancreas. We speculate that increased β-cell responsiveness (insulin secretion) following increased amino acid supply may be due to increased generation of secondary messengers in the β-cell. This may be enhanced by the paracrine action of glucagon on the β-cell.

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Section: Discussionmentioning

confidence: 85%

Increased amino acid supply potentiates glucose-stimulated insulin secretion but does not increase β-cell mass in fetal sheep

Gadhia

Maliszewski

O'Meara

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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“…In addition, norepinephrine concentrations were negatively associated with fetal blood oxygen content (27), indicating that, during chronic exposure to hypoxia, norepinephrine release is tightly regulated by fetal blood oxygen content. In contrast to the placental insufficiency group, fetal sheep exposed only to chronic hypoglycemia did not have decreased blood oxygen content or elevated plasma norepinephrine concentrations (23). Therefore, we postulated that the disparity in insulin secretion between fetuses with placental insufficiency and those with experimental hypoglycemia reflects a suppressive action from norepinephrine.…”

mentioning

confidence: 94%

“…Although these fetuses are hypoglycemic, our research indicates that factors in addition to glucose deficiency likely contribute to the impaired ␤-cell responsiveness. These studies showed that sheep fetuses made experimentally hypoglycemic for 2 wk have only a 45% reduction in glucosestimulated insulin secretion (GSIS), less than half that of the sheep fetuses with placental insufficiency, despite similar plasma glucose concentrations (23,27). Additional causative factors might include time of glucose deficiency onset, duration of glucose deficiency, or other nutrient deficiencies.…”

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confidence: 97%

“…These studies showed that sheep fetuses made experimentally hypoglycemic for 2 wk have only a 45% reduction in glucosestimulated insulin secretion (GSIS), less than half that of the sheep fetuses with placental insufficiency, despite similar plasma glucose concentrations (23, 27). Additional causative factors might include time of glucose deficiency onset, duration of glucose deficiency, or other nutrient deficiencies.One important difference between these two sheep models of IUGR is fetal blood oxygen content, which was significantly lower in fetuses with placental insufficiency (23,27,39). During acute fetal asphyxia or hypoxia caused by maternal hypoxemia, umbilical cord occlusion, or severing the umbilical cord at delivery, plasma norepinephrine concentrations rise (8,20,21,29).…”

mentioning

confidence: 97%

“…One important difference between these two sheep models of IUGR is fetal blood oxygen content, which was significantly lower in fetuses with placental insufficiency (23,27,39). During acute fetal asphyxia or hypoxia caused by maternal hypoxemia, umbilical cord occlusion, or severing the umbilical cord at delivery, plasma norepinephrine concentrations rise (8,20,21,29).…”

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confidence: 97%

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Chronic exposure to elevated norepinephrine suppresses insulin secretion in fetal sheep with placental insufficiency and intrauterine growth restriction

Leos

Anderson

Chen

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

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130

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In this study, we examined chronic norepinephrine suppression of insulin secretion in sheep fetuses with placental insufficiency-induced intrauterine growth restriction (IUGR). Glucose-stimulated insulin secretion (GSIS) was measured with a square-wave hyperglycemic clamp in the presence or absence of adrenergic receptor antagonists phentolamine (alpha) and propranolol (beta). IUGR fetuses were hypoglycemic and hypoxemic and had lower GSIS responsiveness (P < or = 0.05) than control fetuses. IUGR fetuses also had elevated plasma norepinephrine (3,264 +/- 614 vs. 570 +/- 86 pg/ml; P < or = 0.05) and epinephrine (164 +/- 32 vs. 60 +/- 12 pg/ml; P < or = 0.05) concentrations. In control fetuses, adrenergic inhibition increased baseline plasma insulin concentrations (1.7-fold, P < or = 0.05), whereas during hyperglycemia insulin was not different. A greater (P < or = 0.05) response to adrenergic inhibition was found in IUGR fetuses, and the average plasma insulin concentrations increased 4.9-fold at baseline and 7.1-fold with hyperglycemia. Unlike controls, basal plasma glucose concentrations fell (P < or = 0.05) with adrenergic antagonists. GSIS responsiveness, measured by the change in insulin, was higher (8.9-fold, P < or = 0.05) in IUGR fetuses with adrenergic inhibition than controls (1.8-fold, not significant), showing that norepinephrine suppresses insulin secretion in IUGR fetuses. Strikingly, in IUGR fetuses, adrenergic inhibition resulted in a greater GSIS responsiveness, because beta-cell mass was 56% lower and the maximal stimulatory insulin response tended (P < 0.1) to be higher than controls. This persistent norepinephrine suppression appears to be partially explained by higher mRNA concentrations of adrenergic receptors alpha(1D), alpha(2A), and alpha(2B) in a cohort of fetuses that were naïve to the antagonists. Therefore, norepinephrine suppression of insulin secretion was maintained, in part, by upregulating adrenergic receptor expression, but the beta-cells also appeared to compensate with enhanced GSIS. These findings may begin to explain why IUGR infants have a propensity for increased glucose requirements if norepinephrine is suddenly decreased after birth.

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Environmental Heat Stress Impairs Placental Function, Fetal Growth and Development, and Postnatal Performance in Livestock

Yates

Chen

Limesand

2012

Environmental Physiology of Livestock

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Adaptation of ovine fetal pancreatic insulin secretion to chronic hypoglycaemia and euglycaemic correction

Cited by 31 publications

References 54 publications

Increased amino acid supply potentiates glucose-stimulated insulin secretion but does not increase β-cell mass in fetal sheep

Increased amino acid supply potentiates glucose-stimulated insulin secretion but does not increase β-cell mass in fetal sheep

Chronic exposure to elevated norepinephrine suppresses insulin secretion in fetal sheep with placental insufficiency and intrauterine growth restriction

Environmental Heat Stress Impairs Placental Function, Fetal Growth and Development, and Postnatal Performance in Livestock

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