Glucose transporters and glucose utilization in rat brain after acute ethanol administration

Handa, Raj K.; DeJoseph, M. Regina; Singh, Leela D.; Hawkins, Richard A.; Singh, Sant P.

doi:10.1007/bf02674530

Cited by 22 publications

(19 citation statements)

References 39 publications

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“…In addition to regulating glucose utilization, insulin can stimulate glucose uptake. Glucose uptake is mediated by glucose transporter molecules termed GLUTs [73], and previous studies demonstrated that chronic gestational exposure to ethanol inhibits expression and function of GLUT molecules in the brain [74][75][76]. Correspondingly, the present work demonstrated significantly reduced levels of GLUT2 and GLUT4 gene expression, as well as reduced levels of ATP in cerebellar tissue from ethanol-exposed pups.…”

Section: Effects Of Ethanol On Insulin and Igf-i Rtk Activitiessupporting

confidence: 67%

Ethanol inhibits insulin expression and actions in the developing brain

Monte

Wands

2005

CMLS, Cell. Mol. Life Sci.

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Ethanol-induced cerebellar hypoplasia is associated with inhibition of insulin-stimulated survival signaling. The present work explores the mechanisms of impaired insulin signaling in a rat model of fetal alcohol syndrome. Real-time quantitative RT-PCR demonstrated reduced expression of the insulin gene in cerebella of ethanol-exposed pups. Although receptor expression was unaffected, insulin and insulin-like growth factor (IGF-I) receptor tyrosine kinase (RTK) activities were reduced by ethanol exposure, and these abnormalities were associated with increased PTP1b activity. In addition, glucose transporter molecule expression and steady-state levels of ATP were reduced in ethanol-exposed cerebellar tissue. Cultured cerebellar granule neurons from ethanol-exposed pups had reduced expression of genes encoding insulin, IGF-II, and the IGF-I and IGF-II receptors, and impaired insulin- and IGF-I-stimulated glucose uptake and ATP production. The results demonstrate that ethanol inhibits insulin-mediated actions in the developing brain by reducing local insulin production and insulin RTK activation, leading to inhibition of glucose transport and ATP production.

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Section: Effects Of Ethanol On Insulin and Igf-i Rtk Activitiessupporting

confidence: 67%

Ethanol inhibits insulin expression and actions in the developing brain

Monte

Wands

2005

CMLS, Cell. Mol. Life Sci.

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“…In sheep and humans, fetal glucose is almost entirely acquired from the mother via the placenta (2,18) and one would expect that decreases in maternal blood glucose would be reflected by a similar decrease in fetal blood glucose. The lack of substantial hypoxemia in the fetus following EtOH exposure could be a result of decreased fetal glucose utilization; EtOH is known to inhibit fetal glucose transporters GLUT1 and GLUT3 (15,34). Decreased fetal glucose uptake and utilization could explain the observed trend toward a reduction in ponderal index in our EtOH-treated fetuses.…”

Section: Fetal Blood Glucose Concentrationsmentioning

confidence: 53%

Daily ethanol exposure during late ovine pregnancy: physiological effects in the mother and fetus in the apparent absence of overt fetal cerebral dysmorphology

Kenna

Matteo

Hanita

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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High levels of ethanol (EtOH) consumption during pregnancy adversely affect fetal development; however, the effects of lower levels of exposure are less clear. Our objectives were to assess the effects of daily EtOH exposure (3.8 USA standard drinks) on fetal-maternal physiological variables and the fetal brain, particularly white matter. Pregnant ewes received daily intravenous infusions of EtOH (0.75 g/kg maternal body wt over 1 h, 8 fetuses) or saline (8 fetuses) from 95 to 133 days of gestational age (DGA; term ∼145 DGA). Maternal and fetal arterial blood was sampled at 131-133 DGA. At necropsy (134 DGA) fetal brains were collected for analysis. Maternal and fetal plasma EtOH concentrations reached similar maximal concentration (∼0.11 g/dl) and declined at the same rate. EtOH infusions produced mild reductions in fetal arterial oxygenation but there were no changes in maternal oxygenation, maternal and fetal Pa(CO(2)), or in fetal mean arterial pressure or heart rate. Following EtOH infusions, plasma lactate levels were elevated in ewes and fetuses, but arterial pH fell only in ewes. Fetal body and brain weights were similar between groups. In three of eight EtOH-exposed fetuses there were small subarachnoid hemorrhages in the cerebrum and cerebellum associated with focal cortical neuronal death and gliosis. Overall, there was no evidence of cystic lesions, inflammation, increased apoptosis, or white matter injury. We conclude that daily EtOH exposure during the third trimester-equivalent of ovine pregnancy has modest physiological effects on the fetus and no gross effects on fetal white matter development.

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“…Ethanol may also impair fetal tissue uptake of nutrients from the fetal circulation, for example by decreasing the expression and activity of glucose transporters. Ethanol administration to adult rats rapidly decreases plasma membrane abundance of GLUT1 and GLUT3 in the cerebral cortex (19), and GLUT1 expression and in vivo and in vitro glucose uptake are reduced in brain tissue of ethanol-exposed fetal rats (37,38). These studies suggest that both impaired placental transport of nutrients and impaired fetal tissue uptake of nutrients may contribute to fetal growth restriction caused by acute ethanol exposure.…”

Section: Discussionmentioning

confidence: 78%