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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003ESkeletal muscle is the major site for insulin-dependent glucose utilization, and insulin resistance in skeletal muscle is thought to be integral in the pathogenesis of type 2 diabetes mellitus (T2DM). This article discusses some emerging insights into the molecular basis of skeletal muscle insulin resistance, highlighting the role of peroxisome proliferator activated receptor-gamma (PPAR-?), a nuclear transcription factor.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EInsulin\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes Mellitus\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EInsulin\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EEndocrinology\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes \u0026amp; Metabolic Syndrome\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes Mellitus\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003ESkeletal muscle is the major site for insulin-dependent glucose utilization, and insulin resistance in skeletal muscle is thought to be integral in the pathogenesis of type 2 diabetes mellitus (T2DM). Kyong Soo Park, MD, PhD, Seoul National University, Seoul, South Korea, discussed some emerging insights into the molecular basis of skeletal muscle insulin resistance, highlighting the role of peroxisome proliferator activated receptor-gamma (PPAR-\u03b3), a nuclear transcription factor.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EPPAR-\u03b3 is implicated in the regulation of fat metabolism in skeletal muscle, and is activated by the binding of specific ligands, including thiazolidinediones (TZDs), such as troglitazone, rosiglitazone, and pioglitazone, which are used for the treatment of T2DM [Chung SS et al. \u003Cem\u003EMol Cell Biol\u003C\/em\u003E 2009]. Although PPAR-\u03b3 is mostly expressed in fat tissue where it is critically involved in lipogenesis and adipocyte differentiation, low levels are also expressed in skeletal muscle where it enhances insulin sensitivity [Chung SS et al. \u003Cem\u003EBiochem J\u003C\/em\u003E 2011].\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EOxidative stress plays a central role in the pathogenesis of insulin resistance, T2DM, and its vascular complications. Production of reactive oxygen species is increased in T2DM, and antioxidant activity is simultaneously reduced. TZDs, however, have been shown to prevent oxidative stress-induced insulin resistance in skeletal muscle. They activate PPAR-\u03b3, stimulating glutathione peroxidase 3 (GPx3) gene expression leading to reduction of extracellular hydrogen peroxide (H\u003Csub\u003E2\u003C\/sub\u003EO\u003Csub\u003E2\u003C\/sub\u003E) levels that contribute to insulin resistance in skeletal muscle cells. Since inhibition of GPx3 expression prevents this TZD-induced antioxidant effect, GPx3 is thought to be essential for the regulation of PPAR-\u03b3-mediated antioxidant activity. And since lower GPx3 levels have also been demonstrated in patients with T2DM and in diabetic diet-induced obese mice, the antioxidant effect of PPAR-\u03b3 is considered to be completely mediated by GPx3 [Chung SS et al. \u003Cem\u003EMol Cell Biol\u003C\/em\u003E 2009].\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EMore recently, the function of PPAR-\u03b3 has been shown to be regulated by various posttranslational modifications, including SUMOylation, which involves binding of a small ubiquitin-like modifier (SUMO) protein to target proteins. SUMOylation is catalyzed by SUMO-specific proteases (SENPs). In one study of C2C12 cells in a primary line of mouse myoblasts, the critical role of SENP2 in lipogenesis as a desumoylating enzyme was demonstrated. SENP2 effectively removed SUMO from PPAR-\u03b3-SUMO conjugates, while also increasing PPAR-\u03b3 transcriptional activity. In addition, SENP2 overexpression selectively enhanced the expression of the PPAR-\u03b3 target genes FABP3 (fatty-acid-binding protein 3) and CD36 (fatty acid translocase), in the presence and absence of rosiglitazone, but had no effect on ADRP (adipose differentiation-related protein) [Chung SS et al. \u003Cem\u003EBiochem J\u003C\/em\u003E 2011].\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EProf. Park emphasized the important role that GPx3 plays in regulating oxidative stress, and its potential as a therapeutic target for both insulin resistance and T2DM. In addition, he also noted the potential for SENP2 as a potential therapeutic target to deal with excess fatty acids in skeletal muscle.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2013 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/13\/16\/12.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nznm5e\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}