bims-exemet 2021-07-11 papers

Issue of 2021–07–11
three papers selected by
Javier Botella Ruiz, Victoria University

Lipids Health Dis. 2021 Jul 06. 20(1): 64

The effects of exercise training versus intensive insulin treatment on skeletal muscle fibre content in type 1 diabetes mellitus rodents.

David P McBey, Michelle Dotzert, C W J Melling.

BACKGROUND: Intensive-insulin treatment (IIT) strategy for patients with type 1 diabetes mellitus (T1DM) has been associated with sedentary behaviour and the development of insulin resistance. Exercising patients with T1DM often utilize a conventional insulin treatment (CIT) strategy leading to increased insulin sensitivity through improved intramyocellular lipid (IMCL) content. It is unclear how these exercise-related metabolic adaptations in response to exercise training relate to individual fibre-type transitions, and whether these alterations are evident between different insulin strategies (CIT vs. IIT).
PURPOSE: This study examined glycogen and fat content in skeletal muscle fibres of diabetic rats following exercise-training.
METHODS: Male Sprague-Dawley rats were divided into four groups: Control-Sedentary, CIT- and IIT-treated diabetic sedentary, and CIT-exercised trained (aerobic/resistance; DARE). After 12 weeks, muscle-fibre lipids and glycogen were compared through immunohistochemical analysis.
RESULTS: The primary findings were that both IIT and DARE led to significant increases in type I fibres when compared to CIT, while DARE led to significantly increased lipid content in type I fibres compared to IIT.
CONCLUSIONS: These findings indicate that alterations in lipid content with insulin treatment and DARE are primarily evident in type I fibres, suggesting that muscle lipotoxicity in type 1 diabetes is muscle fibre-type dependant.

Keywords: Exercise; Insulin treatment; Intramyocellular lipids; Muscle glycogen; Skeletal muscle fibre; Type 1 diabetes mellitus

DOI: https://doi.org/10.1186/s12944-021-01494-w

Front Immunol. 2021 ;12 702025

Exercise Counterbalances Rho/ROCK2 Signaling Impairment in the Skeletal Muscle and Ameliorates Insulin Sensitivity in Obese Mice.

Vitor R Muñoz, Rafael C Gaspar, Matheus B Severino, Ana P A Macêdo, Fernando M Simabuco, Eduardo R Ropelle, Dennys E Cintra, Adelino S R da Silva, Young-Bum Kim, José Rodrigo Pauli.

Physical exercise is considered a fundamental strategy in improving insulin sensitivity and glucose uptake in skeletal muscle. However, the molecular mechanisms underlying this regulation, primarily on skeletal muscle glucose uptake, are not fully understood. Recent evidence has shown that Rho-kinase (ROCK) isoforms play a pivotal role in regulating skeletal muscle glucose uptake and systemic glucose homeostasis. The current study evaluated the effect of physical exercise on ROCK2 signaling in skeletal muscle of insulin-resistant obese animals. Physiological (ITT) and molecular analysis (immunoblotting, and RT-qPCR) were performed. The contents of RhoA and ROCK2 protein were decreased in skeletal muscle of obese mice compared to control mice but were restored to normal levels in response to physical exercise. The exercised animals also showed higher phosphorylation of insulin receptor substrate 1 (IRS1 Serine 632/635) and protein kinase B (Akt) in the skeletal muscle. However, phosphatase and tensin homolog (PTEN) and protein-tyrosine phosphatase-1B (PTP-1B), both inhibitory regulators for insulin action, were increased in obesity but decreased after exercise. The impact of ROCK2 action on muscle insulin signaling is further underscored by the fact that impaired IRS1 and Akt phosphorylation caused by palmitate in C2C12 myotubes was entirely restored by ROCK2 overexpression. These results suggest that the exercise-induced upregulation of RhoA-ROCK2 signaling in skeletal muscle is associated with increased systemic insulin sensitivity in obese mice and further implicate that muscle ROCK2 could be a potential target for treating obesity-linked metabolic disorders.

Keywords: Rho-kinase (ROCK); exercise; insulin sensitivity; obesity; skeletal muscle

DOI: https://doi.org/10.3389/fimmu.2021.702025

iScience. 2021 Jul 23. 24(7): 102712

Skeletal muscle proteomes reveal downregulation of mitochondrial proteins in transition from prediabetes into type 2 diabetes.

Tiina Öhman, Jaakko Teppo, Neeta Datta, Selina Mäkinen, Markku Varjosalo, Heikki A Koistinen.

Skeletal muscle insulin resistance is a central defect in the pathogenesis of type 2 diabetes (T2D). Here, we analyzed skeletal muscle proteome in 148 vastus lateralis muscle biopsies obtained from men covering all glucose tolerance phenotypes: normal, impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and T2D. Skeletal muscle proteome was analyzed by a sequential window acquisition of all theoretical mass spectra (SWATH-MS) proteomics technique. Our data indicate a downregulation in several proteins involved in mitochondrial electron transport or respiratory chain complex assembly already in IFG and IGT muscles, with most profound decreases observed in T2D. Additional phosphoproteomic analysis reveals altered phosphorylation in several signaling pathways in IFG, IGT, and T2D muscles, including those regulating glucose metabolic processes, and the structure of muscle cells. These data reveal several alterations present in skeletal muscle already in prediabetes and highlight impaired mitochondrial energy metabolism in the trajectory from prediabetes into T2D.

Keywords: Diabetology; Molecular biology; Proteomics

DOI: https://doi.org/10.1016/j.isci.2021.102712