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BMC Endocrine Disorders
Published in: BMC Endocrine Disorders 1/2021

01-12-2021 | Insulins | Research article

Relationship between insulin sensitivity and gene expression in human skeletal muscle

Authors: Hemang M. Parikh, Targ Elgzyri, Amra Alibegovic, Natalie Hiscock, Ola Ekström, Karl-Fredrik Eriksson, Allan Vaag, Leif C. Groop, Kristoffer Ström, Ola Hansson

Published in: BMC Endocrine Disorders | Issue 1/2021

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Abstract

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.
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Metadata
Title
Relationship between insulin sensitivity and gene expression in human skeletal muscle
Authors
Hemang M. Parikh
Targ Elgzyri
Amra Alibegovic
Natalie Hiscock
Ola Ekström
Karl-Fredrik Eriksson
Allan Vaag
Leif C. Groop
Kristoffer Ström
Ola Hansson
Publication date
01-12-2021
Publisher
BioMed Central
Keywords
Insulins
Insulins
Published in
BMC Endocrine Disorders / Issue 1/2021
Electronic ISSN: 1472-6823
DOI
https://doi.org/10.1186/s12902-021-00687-9

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