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: db07-0155v1 56/11/2710    most recent Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Poulsen, P. Articles by Vaag, A. Search for Related Content PubMed PubMed Citation Articles by Poulsen, P. Articles by Vaag, A. Social Bookmarking                What's this?

Low Birth Weight and Zygosity Status Is Associated With Defective Muscle Glycogen and Glycogen Synthase Regulation in Elderly Twins

¹ Steno Diabetes Center, Gentofte, Denmark
² Copenhagen Muscle Research Centre, Institute of Exercise and Sport Sciences, University of Copenhagen, Copenhagen, Denmark
³ Odense University Hospital, Odense, Denmark

Address correspondence and reprint requests to Dr. Pernille Poulsen, Steno Diabetes Center, Niels Steensens Vej 2, DK-2820 Gentofte, Denmark. E-mail: pepn{at}steno.dk

Abbreviations: GS, glycogen synthase; GSK, GS kinase; NOGM, nonoxidative glucose metabolism

OBJECTIVE— An adverse intrauterine environment indicated by both low birth weight and monozygosity is associated with an age- or time-dependent reduction in glucose disposal and nonoxidative glucose metabolism in twins, suggesting impaired regulation of muscle glycogen synthesis.

RESEARCH DESIGN AND METHODS— We measured the activities of glycogen synthase (GS), GS kinase (GSK)3, GS phosphorylation, and glycogen levels in muscle biopsies obtained from 184 young and elderly twins before and after a euglycemic-hyperinsulinemic clamp.

RESULTS— Elderly monozygotic twins had significantly lower fractional GS activity amidst higher glycogen and GS protein levels compared with dizygotic twins. In addition, we demonstrated strong nongenetic associations between birth weight and defect muscle glycogen metabolism in elderly—but not in younger—twins. Thus, for every 100 g increase in birth weight within pairs, GS fractional activity, GS protein level, and glycogen content was increased by 4.2, 8.7, and 4.5%, respectively, in elderly twins. Similarly, for every 100 g increase in birth weight, GSK3 activity and GS phosphorylation at the sites 2, 2+2a, and 3a+3b were decreased by 3.1, 9.0, 10.1, and 9.5%, respectively.

CONCLUSIONS— The age- or time-dependent nongenetic impact of birth weight on insulin action in twins may partly be explained by reduced insulin activation of muscle GS, mediated through increased GSK3 activity and GS phosphorylation. Reduced GS activity and negative feedback inhibition of glycogen metabolism by glycogen per se may contribute to the insulin resistance in elderly monozygotic compared with dizygotic twins.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?