HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 292/5/R1926    most recent 00822.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yao, X.-H. Articles by Grégoire Nyomba, B. L. Search for Related Content PubMed PubMed Citation Articles by Yao, X.-H. Articles by Grégoire Nyomba, B. L.

DEVELOPMENTAL PHYSIOLOGY AND PREGNANCY

Abnormal glucose homeostasis in adult female rat offspring after intrauterine ethanol exposure

Departments of ¹Internal Medicine and ²Physiology, University of Manitoba, Winnipeg, Manitoba, Canada

Submitted 21 November 2006 ; accepted in final form 8 January 2007

Adverse events during pregnancy, including prenatal ethanol (EtOH) exposure, are associated with insulin-resistant diabetes in male rat offspring, but it is unclear whether this is true for female offspring. We investigated whether prenatal EtOH exposure alters glucose metabolism in adult female rat offspring and whether this is associated with reduced in vivo insulin signaling in skeletal muscle. Female Sprague-Dawley rats were given EtOH, 4 g·kg^–1·day^–1 by gavage throughout pregnancy. Glucose tolerance test and hyperinsulinemic euglycemic clamp were performed, and insulin signaling was investigated in skeletal muscle, in adult female offspring. We gave insulin intravenously to these rats and determined the association of glucose transporter-4 with plasma membranes, as well as the phosphorylation of phosphoinositide-dependent protein kinase-1 (PDK1), Akt, and PKC. Although EtOH offspring had normal birth weight, they were overweight as adults and had fasting hyperglycemia, hyperinsulinemia, and reduced insulin-stimulated glucose uptake. After insulin treatment, EtOH-exposed rats had decreased membrane glucose transporter-4, PDK1, Akt, and PKC in the gastrocnemius muscle, compared with control rats. Insulin stimulation of PDK1, Akt, and PKC phosphorylation was also reduced. In addition, the expression of the protein tribbles-3 and the phosphatase enzyme activity of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), which prevent Akt activation, were increased in muscle from EtOH-exposed rats. Female rat offspring exposed to EtOH in utero develop insulin-resistant diabetes in association with excessive PTEN and tribbles-3 signaling downstream of the phosphatidylinositol 3-kinase pathway in skeletal muscle, which may be a mechanism for the abnormal glucose tolerance.

ethanol; intrauterine environment; insulin resistance; Akt; protein kinase C; glucose transporter

This article has been cited by other articles:

				X.-H. Yao and B. L. G. Nyomba Hepatic insulin resistance induced by prenatal alcohol exposure is associated with reduced PTEN and TRB3 acetylation in adult rat offspring Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2008; 294(6): R1797 - R1806. [Abstract] [Full Text] [PDF]