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1 Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada; Department of Pharmacology, Jilin University, Changchun, Jilin, China
2 Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
3 Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada; Department of Physiology, University of Manitoba, Winnipeg, Manitoba, Canada
* To whom correspondence should be addressed. E-mail: bnyomba{at}cc.umanitoba.ca.
It is now known that prenatal ethanol (EtOH) exposure is associated with impaired glucose tolerance and insulin resistance in the rat offspring, but the underlying
mechanism(s) is not known. To test the hypothesis that in vivo insulin signaling through PI 3-kinase is reduced in skeletal muscle of adult rat offspring exposed to EtOH in utero, we gave insulin intravenously to these rats and probed steps in the PI 3-kinase insulin signaling pathway. Following insulin treatment, EtOH-exposed rats had decreased tyrosine phosphorylation of the insulin receptor
-subunit and of insulin receptor substrate-1 (IRS-1), as well as reduced IRS-1-associated PI 3-kinase in the gastrocnemius muscle, compared with control rats. There was no significant difference in basal or insulin-stimulated Akt activity between EtOH-exposed rats and controls. Insulinstimulated PKC
phosphorylation and membrane association were reduced in EtOHexposed
rats compared with controls. Muscle insulin binding and peptide contents of insulin receptor, IRS-1, p85 subunit of PI 3-kinase, Akt/protein kinase B and atypical
protein kinase C isoform
(PKC
) were not different between EtOH-exposed rats and controls. Thus, insulin resistance in rat offspring exposed to EtOH in utero may be explained, at least in part, by impaired insulin signaling through the PI-3 kinase pathway
in skeletal muscle.
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