Relationship between insulin sensitivity and gene expression in human skeletal muscle
Parikh, Hemang M LU ; Elgzyri, Targ LU ; Alibegovic, Amra ; Hiscock, Natalie ; Ekström, Ola LU ; Eriksson, Karl-Fredrik LU ; Vaag, Allan LU ; Groop, Leif C LU ; Ström, Kristoffer LU and Hansson, Ola LU
(2021)
In BMC Endocrine Disorders
21(1).
- 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... (More)
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.
(Less)
- author
- Parikh, Hemang M
LU
; Elgzyri, Targ
LU
; Alibegovic, Amra
; Hiscock, Natalie
; Ekström, Ola
LU
; Eriksson, Karl-Fredrik
LU
; Vaag, Allan
LU
; Groop, Leif C
LU
; Ström, Kristoffer
LU
and Hansson, Ola
LU
- organization
- publishing date
- 2021-02-27
- type
- Contribution to journal
- publication status
- published
- subject
- in
- BMC Endocrine Disorders
- volume
- 21
- issue
- 1
- pages
- 12 pages
- publisher
- BioMed Central (BMC)
- external identifiers
-
- scopus:85101860000
- pmid:33639916
- ISSN
- 1472-6823
- DOI
- 10.1186/s12902-021-00687-9
- language
- English
- LU publication?
- yes
- id
- 78bb3f0f-2039-40e5-9d41-33c38284d699
- date added to LUP
- 2021-03-03 21:59:00
- date last changed
- 2024-06-13 07:42:08
@article{78bb3f0f-2039-40e5-9d41-33c38284d699,
abstract = {{<p>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.</p><p>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).</p><p>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.</p><p>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.</p>}},
author = {{Parikh, Hemang M and Elgzyri, Targ and Alibegovic, Amra and Hiscock, Natalie and Ekström, Ola and Eriksson, Karl-Fredrik and Vaag, Allan and Groop, Leif C and Ström, Kristoffer and Hansson, Ola}},
issn = {{1472-6823}},
language = {{eng}},
month = {{02}},
number = {{1}},
publisher = {{BioMed Central (BMC)}},
series = {{BMC Endocrine Disorders}},
title = {{Relationship between insulin sensitivity and gene expression in human skeletal muscle}},
url = {{http://dx.doi.org/10.1186/s12902-021-00687-9}},
doi = {{10.1186/s12902-021-00687-9}},
volume = {{21}},
year = {{2021}},
}