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Genetic and nongenetic determinants of skeletal muscle glucose transporter 4 messenger ribonucleic acid levels and insulin action in twins

Storgaard, H; Poulsen, P; Ling, Charlotte LU ; Groop, Leif LU and Vaag, A A (2006) In Journal of Clinical Endocrinology and Metabolism 91(2). p.702-708
Abstract
Context: Insulin-stimulated glucose uptake in skeletal muscle is mediated through translocation of the insulin-sensitive glucose transporter 4 ( GLUT4)-containing vesicles to the plasma membrane. Thus, skeletal muscle GLUT4 content plays an important role in whole-body insulin sensitivity. Objectives: The objectives of this study were 1) to examine the relative impact of genetic vs. environmental factors on skeletal muscle GLUT4 mRNA expression using biometric modeling, and 2) to identify factors influencing the expression of GLUT4 and insulin-stimulated whole-body metabolism. Design: We measured GLUT4 mRNA expression in biopsies from young and elderly monozygotic (MZ) and dizygotic (DZ) twins before and during a 2-h hyperinsulinemic... (More)
Context: Insulin-stimulated glucose uptake in skeletal muscle is mediated through translocation of the insulin-sensitive glucose transporter 4 ( GLUT4)-containing vesicles to the plasma membrane. Thus, skeletal muscle GLUT4 content plays an important role in whole-body insulin sensitivity. Objectives: The objectives of this study were 1) to examine the relative impact of genetic vs. environmental factors on skeletal muscle GLUT4 mRNA expression using biometric modeling, and 2) to identify factors influencing the expression of GLUT4 and insulin-stimulated whole-body metabolism. Design: We measured GLUT4 mRNA expression in biopsies from young and elderly monozygotic (MZ) and dizygotic (DZ) twins before and during a 2-h hyperinsulinemic euglycemic clamp including 3-H-3-tritiated glucose and indirect calorimetry. Participants: A random sample of young (22-31 yr; n = 89) and elderly (57 - 66 yr; n = 69) same sex MZ and DZ twin pairs identified through the Danish Twin Register were studied. Results: We found a major genetic component in the control of basal and insulin-stimulated GLUT4 mRNA expression in young and elderly twins. GLUT4 gene expression increased upon insulin stimulation in both young and elderly twins. Multiple regression analysis revealed that both basal and insulin-stimulated GLUT4 mRNA expressions were positively related to birth weight and total body aerobic capacity and were higher in MZ vs. DZ twins as well as in males vs. females. Both basal and insulin-stimulated expressions of GLUT4 were independently and significantly related to whole-body in vivo insulin action, nonoxidative glucose metabolism, and glucose oxidation. Conclusion: We show that skeletal muscle GLUT4 gene expression in twins is significantly and independently related to glucose metabolism and is determined by both genetic and nongenetic factors, including zygosity and birth weight. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Clinical Endocrinology and Metabolism
volume
91
issue
2
pages
702 - 708
publisher
The Endocrine Society
external identifiers
  • wos:000235161200054
  • pmid:16291707
  • scopus:32544445975
ISSN
1945-7197
DOI
10.1210/jc.2005-1172
language
English
LU publication?
yes
id
753a4ed8-91db-4d07-b6f6-3faca77c3c7f (old id 417792)
date added to LUP
2007-10-19 14:09:10
date last changed
2019-03-12 02:48:14
@article{753a4ed8-91db-4d07-b6f6-3faca77c3c7f,
  abstract     = {Context: Insulin-stimulated glucose uptake in skeletal muscle is mediated through translocation of the insulin-sensitive glucose transporter 4 ( GLUT4)-containing vesicles to the plasma membrane. Thus, skeletal muscle GLUT4 content plays an important role in whole-body insulin sensitivity. Objectives: The objectives of this study were 1) to examine the relative impact of genetic vs. environmental factors on skeletal muscle GLUT4 mRNA expression using biometric modeling, and 2) to identify factors influencing the expression of GLUT4 and insulin-stimulated whole-body metabolism. Design: We measured GLUT4 mRNA expression in biopsies from young and elderly monozygotic (MZ) and dizygotic (DZ) twins before and during a 2-h hyperinsulinemic euglycemic clamp including 3-H-3-tritiated glucose and indirect calorimetry. Participants: A random sample of young (22-31 yr; n = 89) and elderly (57 - 66 yr; n = 69) same sex MZ and DZ twin pairs identified through the Danish Twin Register were studied. Results: We found a major genetic component in the control of basal and insulin-stimulated GLUT4 mRNA expression in young and elderly twins. GLUT4 gene expression increased upon insulin stimulation in both young and elderly twins. Multiple regression analysis revealed that both basal and insulin-stimulated GLUT4 mRNA expressions were positively related to birth weight and total body aerobic capacity and were higher in MZ vs. DZ twins as well as in males vs. females. Both basal and insulin-stimulated expressions of GLUT4 were independently and significantly related to whole-body in vivo insulin action, nonoxidative glucose metabolism, and glucose oxidation. Conclusion: We show that skeletal muscle GLUT4 gene expression in twins is significantly and independently related to glucose metabolism and is determined by both genetic and nongenetic factors, including zygosity and birth weight.},
  author       = {Storgaard, H and Poulsen, P and Ling, Charlotte and Groop, Leif and Vaag, A A},
  issn         = {1945-7197},
  language     = {eng},
  number       = {2},
  pages        = {702--708},
  publisher    = {The Endocrine Society},
  series       = {Journal of Clinical Endocrinology and Metabolism},
  title        = {Genetic and nongenetic determinants of skeletal muscle glucose transporter 4 messenger ribonucleic acid levels and insulin action in twins},
  url          = {http://dx.doi.org/10.1210/jc.2005-1172},
  volume       = {91},
  year         = {2006},
}