Cigarette smoke exposure severely reduces peripheral insulin sensitivity without changing GLUT4 expression in oxidative muscle of Wistar rats

Ebersbach-Silva, Patricia; Alves, Thâmara; Fonseca, Ágatha Tomoko Sakata; Oliveira, Marcia Aparecida do Nascimento; Machado, Ubiratan Fabres; Seraphim, Patrícia Monteiro

doi:10.1590/s0004-27302013000100003

Cited by 11 publications

(13 citation statements)

References 30 publications

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“…Dr. Gerald Reaven was the first to identify a relationship between smoking and insulin resistance over 20 years ago (22), and his initial findings have been corroborated by multiple studies since then (4,10,19). Although previous findings may reveal a mechanism (i.e., insulin resistance) whereby smoking results in systemic diseases (17,27), the ensuing decades have failed to implicate a mediating molecular process linking smoking and insulin resistance.…”

Section: Discussionmentioning

confidence: 99%

Ceramides mediate cigarette smoke-induced metabolic disruption in mice

Thatcher

Tippetts

Nelson

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

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Cigarette smoke exposure increases lung ceramide biosynthesis and alters metabolic function. We hypothesized that ceramides are released from the lung during cigarette smoke exposure and result in elevated skeletal muscle ceramide levels, resulting in insulin resistance and altered mitochondrial respiration. Employing cell and animal models, we explored the effect of cigarette smoke on muscle cell insulin signaling and mitochondrial respiration. Muscle cells were treated with conditioned medium from cigarette smoke extract (CSE)-exposed lung cells, followed by analysis of ceramides and assessment of insulin signaling and mitochondrial function. Mice were exposed to daily cigarette smoke and a high-fat, high-sugar (HFHS) diet with myriocin injections to inhibit ceramide synthesis. Comparisons were conducted between these mice and control animals on standard diets in the absence of smoke exposure and myriocin injections. Muscle cells treated with CSE-exposed conditioned medium were completely unresponsive to insulin stimulation, and mitochondrial respiration was severely blunted. These effects were mitigated when lung cells were treated with the ceramide inhibitor myriocin prior to and during CSE exposure. In mice, daily cigarette smoke exposure and HFHS diet resulted in insulin resistance, which correlated with elevated ceramides. Although myriocin injection was protective against insulin resistance with either smoke or HFHS, it was insufficient to prevent insulin resistance with combined CS and HFHS. However, myriocin injection restored muscle mitochondrial respiration in all treatments. Ceramide inhibition prevents metabolic disruption in muscle cells with smoke exposure and may explain whole body insulin resistance and mitochondrial dysfunction in vivo.

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Section: Discussionmentioning

confidence: 99%

Ceramides mediate cigarette smoke-induced metabolic disruption in mice

Thatcher

Tippetts

Nelson

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

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“…The insulin receptor substrate-1 (IRS-1)/protein kinase B (AKT) signal pathway is a crucial classical insulin signal pathway in glucose metabolism [ 29 ]. Glucose and insulin homeostasis are disrupted when the IRS-1/AKT signal pathway is suppressed through increasing phosphorylation of IRS-1 at serine residues, as well as decreasing the expression levels of IRS-1/AKT [ 29 , 30 , 31 , 32 , 33 , 34 ]. In addition, the activated PI3K/AKT signal pathway could accelerate redox-sensitive nuclear factor Nrf2 translocation [ 35 , 36 ].…”

Section: Introductionmentioning

confidence: 99%

Airborne PM2.5-Induced Hepatic Insulin Resistance by Nrf2/JNK-Mediated Signaling Pathway

Jing

Zhang

et al. 2017

IJERPH

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Animal and epidemiological studies have suggested that exposure to airborne particulate matter (PM) with an aerodynamic diameter less than 2.5 μm (PM2.5) is associated with the risk of developing type 2 diabetes. However, the mechanism underlying this risk is poorly understood. In the present study, we investigated the effects of PM2.5 exposure on glucose homeostasis and related signaling pathways in mice. Wild-type and nuclear factor erythroid 2-related factor 2 (Nrf2) knockout (Nrf2−/−) C57BL/6 male mice were exposed to either ambient concentrated PM2.5 or filtered air (FA) for 12 weeks through a whole-body PM exposure system. At the end of the exposure, we assessed liver damage, and performed metabolic studies, gene expressions, as well as molecular signal transductions to determine the signaling pathways involving oxidative responses, insulin signaling, and glucose metabolism. Our results indicated that PM2.5 exposure for 12 weeks caused significant liver damage as evidenced by elevated levels of aminotransferase (AST) and alanine aminotransferase (ALT). Furthermore, PM2.5 exposure induced impaired glucose tolerance and inhibited glycogen synthesis, leading to hepatic insulin resistance indicated by higher glucose levels, higher area under the curve (AUC), and homeostasis model assessment of insulin resistance (HOMA-IR) values. We further found that PM2.5 exposure significantly increased the expressions of Nrf2 and Nrf2-regulated antioxidant genes. Moreover, PM2.5 exposure activated the c-Jun N-terminal kinase (JNK) signaling pathway and increased insulin receptor substrate-1 (IRS-1) phosphorylation at Ser307, but reduced protein kinase B phosphorylation at Ser473. Taken together, our study demonstrated PM2.5 exposure triggered Nrf2-mediated oxidative responses and activated the JNK-mediated inhibitory signaling pathway, resulting in hepatic insulin resistance.

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“…Two groups used only the 18s gene [13,28], five used only Actb gene [29][30][31][32][33]. Other authors used the Cyclophilin gene [15,31] and eight authors used Gapdh as a reference gene in their studies [12,14,[34][35][36][37][38][39][40].…”

Section: Genorm Analysismentioning

confidence: 99%

Validation of Reference Genes for qPCR Analysis of Resistance Training and Androgenic Anabolic Steroids on Hypothalamus, Adrenal Gland and Fat Tissue

Pozzi¹,

Le²,

Fern³

et al. 2016

J Steroids Horm Sci

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Background: Real-time quantitative Polymerase Chain Reaction (qPCR) is a technique used for quantification of gene expression and the use of reference genes is very important to normalize the quantification results. Aim:To validate the most suitable reference genes for resistance exercise training (REx) and use of nandrolone decanoate (DECA) in three different rat tissues. Methods:A total of 40 adult male Wistar rats were distributed into four groups: exposed to vehicle three times per week (wk) (CT); eight wk of REx exposed to vehicle three times per wk (T); exposed to DECA three times per wk (D); eight wk of REx exposed to DECA three times per wk (TD). Stability of the following genes was evaluated: beta actin (Actb), alpha Tubulin (Tubulin), Glyceraldehyde-3-phosphate dehydrogenase (Gapdh), Hypoxanthine phosphoribosyltransferase-1 (Hprt1) and 18s Ribossomal RNA (18s) in hypothalamus, adrenal gland and mesenteric fat tissue using GeNorm, NormFinder and BestKeeper software. Results:In hypothalamus and adrenal, all genes were suitable and none was rejected by statistical analysis; however, in fat tissue, Actb, Gapdh and Hprt1 genes were rejected by geNorm but not the others two software. Conclusion:In hypothalamus and adrenal all selected genes analized were stable and can be used for qPCR gene expression analysis. However, in fat tissue we suggest the Tubulin gene as most stable gene.

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Cigarette smoke exposure severely reduces peripheral insulin sensitivity without changing GLUT4 expression in oxidative muscle of Wistar rats

Cited by 11 publications

References 30 publications

Ceramides mediate cigarette smoke-induced metabolic disruption in mice

Ceramides mediate cigarette smoke-induced metabolic disruption in mice

Airborne PM2.5-Induced Hepatic Insulin Resistance by Nrf2/JNK-Mediated Signaling Pathway

Validation of Reference Genes for qPCR Analysis of Resistance Training and Androgenic Anabolic Steroids on Hypothalamus, Adrenal Gland and Fat Tissue

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