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Ethanol inhibits insulin expression and actions in the developing brain.

Abstract
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.
AuthorsS M de la Monte, X J Xu, J R Wands
JournalCellular and molecular life sciences : CMLS (Cell Mol Life Sci) Vol. 62 Issue 10 Pg. 1131-45 (May 2005) ISSN: 1420-682X [Print] Switzerland
PMID15870954 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Insulin
  • Monosaccharide Transport Proteins
  • Receptors, Somatomedin
  • Somatomedins
  • Ethanol
  • Adenosine Triphosphate
  • Protein-Tyrosine Kinases
  • Receptor Protein-Tyrosine Kinases
  • Receptor, Insulin
  • Glucose
Topics
  • Adenosine Triphosphate (metabolism)
  • Animals
  • Animals, Newborn
  • Brain (drug effects, embryology, metabolism)
  • Cerebellum (drug effects, metabolism)
  • Ethanol (pharmacology)
  • Female
  • Fetal Alcohol Spectrum Disorders (genetics, metabolism)
  • Gene Expression Regulation, Developmental (drug effects, genetics)
  • Glucose (metabolism)
  • Insulin (genetics)
  • Models, Animal
  • Monosaccharide Transport Proteins (genetics)
  • Neurons (drug effects, metabolism)
  • Pregnancy
  • Protein-Tyrosine Kinases (metabolism)
  • Rats
  • Rats, Long-Evans
  • Receptor Protein-Tyrosine Kinases (metabolism)
  • Receptor, Insulin (genetics)
  • Receptors, Somatomedin (genetics)
  • Reverse Transcriptase Polymerase Chain Reaction (methods)
  • Somatomedins (genetics)

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