Exploring the Role of Skeletal Muscle in Insulin Resistance: Lessons from Cultured Cells to Animal Models

Feraco, Alessandra; Gorini, Stefania; Armani, Andrea M.; Camajani, Elisabetta; Rizzo, Manfredi; Caprio, Massimiliano

doi:10.3390/ijms22179327

Cited by 40 publications

(31 citation statements)

References 139 publications

(157 reference statements)

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“…Studies have shown that diet-induced obesity increases the expression of T-cell and MHC II molecules in adipose tissue and fat spots in this tissue [65]. Skeletal muscle is an important organ for insulin response; thus, it presents a significant contribution in systemic insulin sensitivity [66]. Hong et al [67] suggested that the obesity condition affects the inflammatory state of skeletal muscle.…”

Section: Different Levels Of Dietary Soybean Oil Modulate Gene Expres...mentioning

confidence: 99%

Differential Gene Expression Associated with Soybean Oil Level in the Diet of Pigs

Fanalli

Silva

Gomes

et al. 2022

Animals

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The aim of this study was to identify the differentially expressed genes (DEG) from the skeletal muscle and liver samples of animal models for metabolic diseases in humans. To perform the study, the fatty acid (FA) profile and RNA sequencing (RNA-Seq) data of 35 samples of liver tissue (SOY1.5, n = 17 and SOY3.0, n = 18) and 36 samples of skeletal muscle (SOY1.5, n = 18 and SOY3.0, n = 18) of Large White pigs were analyzed. The FA profile of the tissues was modified by the diet, mainly those related to monounsaturated (MUFA) and polyunsaturated (PUFA) FA. The skeletal muscle transcriptome analysis revealed 45 DEG (FDR 10%), and the functional enrichment analysis identified network maps related to inflammation, immune processes, and pathways associated with oxidative stress, type 2 diabetes, and metabolic dysfunction. For the liver tissue, the transcriptome profile analysis revealed 281 DEG, which participate in network maps related to neurodegenerative diseases. With this nutrigenomics study, we verified that different levels of soybean oil in the pig diet, an animal model for metabolic diseases in humans, affected the transcriptome profile of skeletal muscle and liver tissue. These findings may help to better understand the biological mechanisms that can be modulated by the diet.

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Section: Different Levels Of Dietary Soybean Oil Modulate Gene Expres...mentioning

confidence: 99%

Differential Gene Expression Associated with Soybean Oil Level in the Diet of Pigs

Fanalli

Silva

Gomes

et al. 2022

Animals

View full text Add to dashboard Cite

show abstract

“…Due to the complex structural arrangement of the skeletal muscle, mouse C2C12 cells represent the most used cellular models to study skeletal muscle in vitro. Evidence shows that C2C12 cells can be considered an appropriate model to investigate skeletal muscle metabolism because C2C12 cells can undergo differentiation into elongated myotubes and express the insulin-responsive GLUT4 protein [ 44 ]. However, it is still possible that data from these cells could be different from that of skeletal muscles in vivo.…”

Section: Discussionmentioning

confidence: 99%

Oxidative Stress as a Contributor to Insulin Resistance in the Skeletal Muscles of Mice with Polycystic Ovary Syndrome

Yao

Zou

Liu

et al. 2022

IJMS

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Polycystic ovarian syndrome (PCOS) is a reproductive, endocrine, and metabolic disorder. Circulating markers of oxidative stress are abnormal in women with PCOS. There is a close relationship between oxidative stress and insulin resistance (IR). However, little information is available about oxidative stress in the skeletal muscles of those affected by PCOS. In this study, PCOS was induced in prepubertal C57BL/6J mice by injection with dehydroepiandrosterone. Oxidative stress biomarkers were then measured in both serum and skeletal muscles. The underlying mechanisms were investigated in C2C12 myotubes treated with testosterone (T). We discovered increased oxidative biomarkers, increased ROS production, and damaged insulin sensitivity in the skeletal muscles of mice with PCOS. High levels of T caused mitochondrial dysfunction and increased ROS levels through the androgen receptor (AR)-nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) signaling pathway in C2C12 cells. Treatment of C2C12 cells with an antioxidant N-acetylcysteine (NAC) decreased T-induced ROS production, improved mitochondrial function, and reversed IR. Administration of NAC to mice with PCOS improved insulin sensitivity in the skeletal muscles of the animals. Hyperandrogenism caused mitochondrial dysfunction and redox imbalance in the skeletal muscles of mice with PCOS. We discovered that oxidative stress contributed to skeletal muscle IR in PCOS. Reducing ROS levels may improve the insulin sensitivity of skeletal muscles in patients with PCOS.

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“…Blood glucose levels will then quickly restore normo-glycaemia due to insulin-stimulated glucose uptake in skeletal muscle (SkM), but also because of reduced glucose production in the liver [ 9 ]. With increasing SkM IR [ 10 , 11 ], eating a carbohydrate-rich meal will lead to an increased insulin secretory response, but blood glucose levels will still take longer to normalize or may remain high [ 9 ]. The molecular mechanisms behind IR involve a complex network of inter-tissue cross-talk and several indirect effects leading to impaired insulin signaling, as reviewed by Roden & Shulman, 2019 [ 9 ], but also summarized in the following sections.…”

Section: Introductionmentioning

confidence: 99%

Potential Mechanisms for How Long-Term Physical Activity May Reduce Insulin Resistance

et al. 2022

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Insulin became available for the treatment of patients with diabetes 100 years ago, and soon thereafter it became evident that the biological response to its actions differed markedly between individuals. This prompted extensive research into insulin action and resistance (IR), resulting in the universally agreed fact that IR is a core finding in patients with type 2 diabetes mellitus (T2DM). T2DM is the most prevalent form of diabetes, reaching epidemic proportions worldwide. Physical activity (PA) has the potential of improving IR and is, therefore, a cornerstone in the prevention and treatment of T2DM. Whereas most research has focused on the acute effects of PA, less is known about the effects of long-term PA on IR. Here, we describe a model of potential mechanisms behind reduced IR after long-term PA to guide further mechanistic investigations and to tailor PA interventions in the therapy of T2DM. The development of such interventions requires knowledge of normal glucose metabolism, and we briefly summarize an integrated physiological perspective on IR. We then describe the effects of long-term PA on signaling molecules involved in cellular responses to insulin, tissue-specific functions, and whole-body IR.

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Exploring the Role of Skeletal Muscle in Insulin Resistance: Lessons from Cultured Cells to Animal Models

Cited by 40 publications

References 139 publications

Differential Gene Expression Associated with Soybean Oil Level in the Diet of Pigs

Differential Gene Expression Associated with Soybean Oil Level in the Diet of Pigs

Oxidative Stress as a Contributor to Insulin Resistance in the Skeletal Muscles of Mice with Polycystic Ovary Syndrome

Potential Mechanisms for How Long-Term Physical Activity May Reduce Insulin Resistance

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