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PMID: 17709892 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

The effect of insulin on expression of genes and biochemical pathways in human skeletal muscle.

Endocrine ·Vol. 31 ·No. 1 ·2007-02-00 ·Pages 5-17

Wu X, Wang J, Cui X, Maianu L, Rhees B, Rosinski J, So WV, Willi SM, Osier MV, Hill HS, Page GP, Allison DB, Martin M, Garvey WT

Abstract

To study the insulin effects on gene expression in skeletal muscle, muscle biopsies were obtained from 20 insulin sensitive individuals before and after euglycemic hyperinsulinemic clamps. Using microarray analysis, we identified 779 insulin-responsive genes. Particularly noteworthy were effects on 70 transcription factors, and an extensive influence on genes involved in both protein synthesis and degradation. The genetic program in skeletal muscle also included effects on signal transduction, vesicular traffic and cytoskeletal function, and fuel metabolic pathways. Unexpected observations were the pervasive effects of insulin on genes involved in interacting pathways for polyamine and S-adenoslymethionine metabolism and genes involved in muscle development. We further confirmed that four insulin-responsive genes, RRAD, IGFBP5, INSIG1, and NGFI-B (NR4A1), were significantly up-regulated by insulin in cultured L6 skeletal muscle cells. Interestingly, insulin caused an accumulation of NGFI-B (NR4A1) protein in the nucleus where it functions as a transcription factor, without translocation to the cytoplasm to promote apoptosis. The role of NGFI-B (NR4A1) as a new potential mediator of insulin action highlights the need for greater understanding of nuclear transcription factors in insulin action.

MeSH Terms
Adult Cells, Cultured DNA-Binding Proteins/metabolism,physiology Female Gene Expression Profiling Gene Expression Regulation/physiology Glucose Clamp Technique Humans Hyperinsulinism/metabolism Insulin/physiology Male Metabolic Networks and Pathways/genetics Middle Aged Muscle, Skeletal/metabolism Nuclear Receptor Subfamily 4, Group A, Member 1 Oligonucleotide Array Sequence Analysis Receptors, Cytoplasmic and Nuclear/metabolism,physiology Receptors, Steroid/metabolism,physiology Reverse Transcriptase Polymerase Chain Reaction Transcription Factors/genetics,metabolism,physiology
Chemicals
DNA-Binding Proteins Insulin NR4A1 protein, human Nuclear Receptor Subfamily 4, Group A, Member 1 Receptors, Cytoplasmic and Nuclear Receptors, Steroid Transcription Factors
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Wu Xuxia
Department of Nutrition Sciences, University of Alabama at Birmingham, 1675 University Boulevard, Birmingham, AL 35294-3360, USA. xuxiawu@uab.edu
Wang Jelai
Cui Xiangqin
Maianu Lidia
Rhees Brian
Rosinski James
So W Venus
Willi Steven M
Osier Michael V
Hill Helliner S
Page Grier P
Allison David B
Martin Mitchell
Garvey W Timothy
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Article Info
Journal
Endocrine
Abbr.
Endocrine
ISSN
1355-008X
DOI
10.1007/s12020-007-0007-x
Email
xuxiawu@uab.edu
Published
2007-02-00
Pages
5-17
Language
English
Region
United States
NLM ID
9434444
Subset
IM
Grants
NIDDK NIH HHS · DK-38765 · United States
NCRR NIH HHS · M01 RR-00032 · United States
NIDDK NIH HHS · P30-DK56336 · United States
Corrections
ErratumIn
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External Links
PubMed source DOI: 10.1007/s12020-007-0007-x View journal details
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