TY - JOUR
T1 - Low birth weight and zygosity status is associated with defective muscle glycogen and glycogen synthase regulation in elderly twins
AU - Poulsen, Pernille
AU - Wojtaszewski, Jørgen F P
AU - Richter, Erik A
AU - Beck-Nielsen, Henning
AU - Vaag, Allan
PY - 2007/11
Y1 - 2007/11
N2 - 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 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.
AB - 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 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.
KW - Adult
KW - Aged
KW - Aging/physiology
KW - Glucose Clamp Technique
KW - Glycogen/metabolism
KW - Glycogen Synthase/metabolism
KW - Glycogen Synthase Kinase 3/metabolism
KW - Humans
KW - Infant, Low Birth Weight
KW - Infant, Newborn
KW - Middle Aged
KW - Muscle, Skeletal/metabolism
KW - Phosphorylation
KW - Twins
KW - Twins, Dizygotic
KW - Twins, Monozygotic
U2 - 10.2337/db07-0155
DO - 10.2337/db07-0155
M3 - Journal article
C2 - 17698598
SN - 0012-1797
VL - 56
SP - 2710
EP - 2714
JO - Diabetes
JF - Diabetes
IS - 11
ER -