Cellular and Molecular Life Sciences CMLS

, Volume 62, Issue 10, pp 1131–1145

Ethanol inhibits insulin expression and actions in the developing brain

Research Article

DOI: 10.1007/s00018-005-4571-z

Cite this article as:
Monte, S.M..., Xu, X.J. & Wands, J.R. CMLS, Cell. Mol. Life Sci. (2005) 62: 1131. doi:10.1007/s00018-005-4571-z

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.

Key words.

Ethanol central nervous system fetal alcohol syndrome insulin receptor tyrosine kinase insulin-like growth factor type I protein tyrosine phosphatase 

Copyright information

© Birkhäuser Verlag, Basel 2005

Authors and Affiliations

  1. 1.Departments of Pathology and Medicine, Pierre Galletti Research BuildingRhode Island HospitalProvidenceUSA

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