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

This Article Full Text Free Full Text (PDF) Free All Versions of this Article: 100/2/642    most recent 01115.2005v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted 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 ISI Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Yao, X.-H. Articles by Nyomba, B. L. G. Search for Related Content PubMed PubMed Citation Articles by Yao, X.-H. Articles by Nyomba, B. L. G.

Adult rats prenatally exposed to ethanol have increased gluconeogenesis and impaired insulin response of hepatic gluconeogenic genes

Departments of ¹Internal Medicine and ²Physiology, University of Manitoba, Winnipeg, Manitoba, Canada; and ³Department of Pharmacology, Jilin University, Changchun, China

Submitted 9 September 2005 ; accepted in final form 12 October 2005

Rat offspring exposed to ethanol (EtOH rats) during pregnancy are insulin resistant, but it is unknown whether they have increased gluconeogenesis. To address this issue, we determined blood glucose and liver gluconeogenic genes, proteins, and enzyme activities before and after insulin administration in juvenile and adult EtOH rats and submitted adult EtOH rats to a pyruvate challenge. In juvenile rats, basal glucose; peroxisome proliferator-activated receptor-coactivator-1 protein and mRNA; and phosphoenolpyruvate carboxykinase enzyme activity, protein, and mRNA were similar between groups. After insulin injection, these parameters failed to decrease in EtOH rats, but glucose decreased by 30% and gluconeogenic enzymes, proteins, and mRNAs decreased by 50–70% in control rats. In adult offspring, basal peroxisome proliferator-activated receptor-coactivator-1 protein and mRNA levels were 40–80% higher in EtOH rats than in controls. Similarly, basal phosphoenolpyruvate carboxykinase activity, protein, and mRNA were 1.8-fold greater in EtOH rats than in controls. These parameters decreased by 50% after insulin injection in control rats, but they remained unchanged in EtOH rats. After insulin injection in the adult rats, glucose decreased by 60% in controls but did not decrease significantly in EtOH rats. A subset of adult EtOH rats had fasting hyperglycemia and an exaggerated glycemic response to pyruvate compared with controls. The data indicate that, after prenatal EtOH exposure, the expression of gluconeogenic genes is exaggerated in adult rat offspring and is insulin resistant in both juvenile and adult rats, explaining increased gluconeogenesis. These alterations persist through adulthood and may contribute to the pathogenesis of Type 2 diabetes after exposure to EtOH in utero.

prenatal ethanol; insulin resistance

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]

				X.-H. Yao and B. L. Gregoire Nyomba Abnormal glucose homeostasis in adult female rat offspring after intrauterine ethanol exposure Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2007; 292(5): R1926 - R1933. [Abstract] [Full Text] [PDF]

				S. Nammi, K. Dembele, and B. L. G. Nyomba Increased 11beta-hydroxysteroid dehydrogenase type-1 and hexose-6-phosphate dehydrogenase in liver and adipose tissue of rat offspring exposed to alcohol in utero Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2007; 292(3): R1101 - R1109. [Abstract] [Full Text] [PDF]

				B. Killingsworth 'Drinking stories' from a playgroup: Alcohol in the lives of middle-class mothers in Australia Ethnography, September 1, 2006; 7(3): 357 - 384. [Abstract] [PDF]

				K. Dembele, X.-H. Yao, L. Chen, and B. L. G. Nyomba Intrauterine ethanol exposure results in hypothalamic oxidative stress and neuroendocrine alterations in adult rat offspring Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2006; 291(3): R796 - R802. [Abstract] [Full Text] [PDF]