Relationship between insulin sensitivity and gene expression in human skeletal muscle

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Parikh , H M , Elgzyri , T , Alibegovic , A , Hiscock , N , Ekstrom , O , Eriksson , K-F , Vaag , A , Groop , L C , Strom , K & Hansson , O 2021 , ' Relationship between insulin sensitivity and gene expression in human skeletal muscle ' , BMC Endocrine Disorders , vol. 21 , no. 1 , 32 .

Title: Relationship between insulin sensitivity and gene expression in human skeletal muscle
Author: Parikh, Hemang M.; Elgzyri, Targ; Alibegovic, Amra; Hiscock, Natalie; Ekstrom, Ola; Eriksson, Karl-Fredrik; Vaag, Allan; Groop, Leif C.; Strom, Kristoffer; Hansson, Ola
Contributor organization: Centre of Excellence in Complex Disease Genetics
Institute for Molecular Medicine Finland
HUS Abdominal Center
Date: 2021-02-27
Language: eng
Number of pages: 12
Belongs to series: BMC Endocrine Disorders
ISSN: 1472-6823
Abstract: BackgroundInsulin 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.MethodsTo 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).ResultsWe 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.ConclusionsThe 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.
Subject: 3121 General medicine, internal medicine and other clinical medicine
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion

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