Low birth weight and zygosity status is associated with defective muscle glycogen and glycogen synthase regulation in elderly twins.
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.


METHODS
We measured the activities of glycogen synthase (GS), GS kinase (GSK)3 alpha, 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 alpha 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 alpha 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.
Poulsen
Pernille
P
Steno Diabetes Center, Niels Steensens Vej 2, DK-2820 Gentofte, Denmark. pepn@steno.dk
Wojtaszewski
Jørgen F P
JF
Richter
Erik A
EA
Beck-Nielsen
Henning
H
Vaag
Allan
A
D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D015309:Glucose Clamp Technique; D006003:Glycogen / Q000378:metabolism*; D006006:Glycogen Synthase / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D010766:Phosphorylation; D014427:Twins; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic
D006003:Glycogen; D006006:Glycogen Synthase; D038362:Glycogen Synthase Kinase 3; C448021:glycogen synthase kinase 3 alpha