PMID- 33639916
OWN - NLM
STAT- MEDLINE
DCOM- 20211102
LR  - 20211102
IS  - 1472-6823 (Electronic)
IS  - 1472-6823 (Linking)
VI  - 21
IP  - 1
DP  - 2021 Feb 27
TI  - Relationship between insulin sensitivity and gene expression in human skeletal 
      muscle.
PG  - 32
LID - 10.1186/s12902-021-00687-9 [doi]
LID - 32
AB  - BACKGROUND: Insulin resistance (IR) in skeletal muscle is a key feature of the 
      pre-diabetic state, hypertension, dyslipidemia, cardiovascular diseases and also 
      predicts type 2 diabetes. However, the underlying molecular mechanisms are still 
      poorly understood. METHODS: To explore these mechanisms, we related global 
      skeletal muscle gene expression profiling of 38 non-diabetic men to a surrogate 
      measure of insulin sensitivity, i.e. homeostatic model assessment of insulin 
      resistance (HOMA-IR). RESULTS: We identified 70 genes positively and 110 genes 
      inversely correlated with insulin sensitivity in human skeletal muscle, 
      identifying autophagy-related genes as positively correlated with insulin 
      sensitivity. Replication in an independent study of 9 non-diabetic men resulted 
      in 10 overlapping genes that strongly correlated with insulin sensitivity, 
      including SIRT2, involved in lipid metabolism, and FBXW5 that regulates mammalian 
      target-of-rapamycin (mTOR) and autophagy. The expressions of SIRT2 and FBXW5 were 
      also positively correlated with the expression of key genes promoting the 
      phenotype of an insulin sensitive myocyte e.g. PPARGC1A. CONCLUSIONS: The muscle 
      expression of 180 genes were correlated with insulin sensitivity. These data 
      suggest that activation of genes involved in lipid metabolism, e.g. SIRT2, and 
      genes regulating autophagy and mTOR signaling, e.g. FBXW5, are associated with 
      increased insulin sensitivity in human skeletal muscle, reflecting a highly 
      flexible nutrient sensing.
FAU - Parikh, Hemang M
AU  - Parikh HM
AUID- ORCID: 0000-0002-9076-6709
AD  - Health Informatics Institute, Morsani College of Medicine, University of South 
      Florida, 3650 Spectrum Blvd, Tampa, FL, 33612, USA. parikhhemangm@gmail.com.
AD  - Department of Clinical Sciences, Diabetes & Endocrinology, Lund University, 
      University Hospital Malmo, SE-20502, Malmo, Sweden. parikhhemangm@gmail.com.
FAU - Elgzyri, Targ
AU  - Elgzyri T
AD  - Department of Clinical Sciences, Diabetes & Endocrinology, Lund University, 
      University Hospital Malmo, SE-20502, Malmo, Sweden.
FAU - Alibegovic, Amra
AU  - Alibegovic A
AD  - Steno Diabetes Center, DK-2820, Gentofte, Denmark.
FAU - Hiscock, Natalie
AU  - Hiscock N
AD  - Unilever Discover R & D, Colworth Science Park, Sharnbrook, Bedfordshire, MK44 
      1LQ, UK.
FAU - Ekstrom, Ola
AU  - Ekstrom O
AD  - Department of Clinical Sciences, Diabetes & Endocrinology, Lund University, 
      University Hospital Malmo, SE-20502, Malmo, Sweden.
FAU - Eriksson, Karl-Fredrik
AU  - Eriksson KF
AD  - Department of Clinical Sciences, Diabetes & Endocrinology, Lund University, 
      University Hospital Malmo, SE-20502, Malmo, Sweden.
FAU - Vaag, Allan
AU  - Vaag A
AD  - Steno Diabetes Center, DK-2820, Gentofte, Denmark.
FAU - Groop, Leif C
AU  - Groop LC
AD  - Department of Clinical Sciences, Diabetes & Endocrinology, Lund University, 
      University Hospital Malmo, SE-20502, Malmo, Sweden.
AD  - Finnish Institute of Molecular Medicine, FI-00014, University of Helsinki, 
      Helsinki, Finland.
FAU - Strom, Kristoffer
AU  - Strom K
AD  - Department of Clinical Sciences, Diabetes & Endocrinology, Lund University, 
      University Hospital Malmo, SE-20502, Malmo, Sweden.
AD  - Swedish Winter Sports Research Centre, Mid Sweden University, SE-83125, 
      Ostersund, Sweden.
FAU - Hansson, Ola
AU  - Hansson O
AD  - Department of Clinical Sciences, Diabetes & Endocrinology, Lund University, 
      University Hospital Malmo, SE-20502, Malmo, Sweden.
AD  - Finnish Institute of Molecular Medicine, FI-00014, University of Helsinki, 
      Helsinki, Finland.
LA  - eng
GR  - Dnr IRC15-0067/LUDC-IRC: Swedish Foundation for Strategic Research/
GR  - Dnr 2009-1039/EXODIAB: Swedish Research Council, Strategic Research Area/
PT  - Journal Article
DEP - 20210227
PL  - England
TA  - BMC Endocr Disord
JT  - BMC endocrine disorders
JID - 101088676
SB  - IM
MH  - Adult
MH  - Cells, Cultured
MH  - Cohort Studies
MH  - Female
MH  - Gene Expression
MH  - Gene Expression Profiling/*methods
MH  - Humans
MH  - Insulin Resistance/*genetics
MH  - Male
MH  - Muscle, Skeletal/*metabolism
MH  - Real-Time Polymerase Chain Reaction/methods
MH  - Sedentary Behavior
PMC - PMC7912896
COIS- The authors declare that there are no conflicts of interest regarding the 
      publication of this article.
EDAT- 2021/03/01 06:00
MHDA- 2021/11/03 06:00
PMCR- 2021/02/27
CRDT- 2021/02/28 20:23
PHST- 2020/07/16 00:00 [received]
PHST- 2021/02/03 00:00 [accepted]
PHST- 2021/02/28 20:23 [entrez]
PHST- 2021/03/01 06:00 [pubmed]
PHST- 2021/11/03 06:00 [medline]
PHST- 2021/02/27 00:00 [pmc-release]
AID - 10.1186/s12902-021-00687-9 [pii]
AID - 687 [pii]
AID - 10.1186/s12902-021-00687-9 [doi]
PST - epublish
SO  - BMC Endocr Disord. 2021 Feb 27;21(1):32. doi: 10.1186/s12902-021-00687-9.