TITLE

An Extract of Artemisia dracunculus L. Inhibits Ubiquitin-Proteasome Activity and Preserves Skeletal Muscle Mass in a Murine Model of Diabetes

AUTHOR(S)
Kirk-Ballard, Heather; Wang, Zhong Q.; Acharya, Priyanka; Zhang, Xian H.; Yu, Yongmei; Kilroy, Gail; Ribnicky, David; Cefalu, William T.; Floyd, Z. Elizabeth
PUB. DATE
February 2013
SOURCE
PLoS ONE;Feb2013, Vol. 8 Issue 2, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Impaired insulin signaling is a key feature of type 2 diabetes and is associated with increased ubiquitin-proteasome-dependent protein degradation in skeletal muscle. An extract of Artemisia dracunculus L. (termed PMI5011) improves insulin action by increasing insulin signaling in skeletal muscle. We sought to determine if the effect of PMI5011 on insulin signaling extends to regulation of the ubiquitin-proteasome system. C2C12 myotubes and the KK-Ay murine model of type 2 diabetes were used to evaluate the effect of PMI5011 on steady-state levels of ubiquitylation, proteasome activity and expression of Atrogin-1 and MuRF-1, muscle-specific ubiquitin ligases that are upregulated with impaired insulin signaling. Our results show that PMI5011 inhibits proteasome activity and steady-state ubiquitylation levels in vitro and in vivo. The effect of PMI5011 is mediated by PI3K/Akt signaling and correlates with decreased expression of Atrogin-1 and MuRF-1. Under in vitro conditions of hormonal or fatty acid-induced insulin resistance, PMI5011 improves insulin signaling and reduces Atrogin-1 and MuRF-1 protein levels. In the KK-Ay murine model of type 2 diabetes, skeletal muscle ubiquitylation and proteasome activity is inhibited and Atrogin-1 and MuRF-1 expression is decreased by PMI5011. PMI5011-mediated changes in the ubiquitin-proteasome system in vivo correlate with increased phosphorylation of Akt and FoxO3a and increased myofiber size. The changes in Atrogin-1 and MuRF-1 expression, ubiquitin-proteasome activity and myofiber size modulated by PMI5011 in the presence of insulin resistance indicate the botanical extract PMI5011 may have therapeutic potential in the preservation of muscle mass in type 2 diabetes.
ACCESSION #
87625212

 

Related Articles

  • Insulin Resistance is Associated with MCP1-Mediated Macrophage Accumulation in Skeletal Muscle in Mice and Humans. Patsouris, David; Cao, Jingwei-Ji; Vial, Guillaume; Bravard, Amelie; Lefai, Etienne; Durand, Annie; Durand, Christine; Chauvin, Marie-Agnés; Laugerette, Fabienne; Debard, Cyrille; Michalski, Marie-Caroline; Laville, Martine; Vidal, Hubert; Rieusset, Jennifer // PLoS ONE;Oct2014, Vol. 9 Issue 10, p1 

    Inflammation is now recognized as a major factor contributing to type 2 diabetes (T2D). However, while the mechanisms and consequences associated with white adipose tissue inflammation are well described, very little is known concerning the situation in skeletal muscle. The aim of this study was...

  • Regulation of ubiquitin-proteasome and autophagy pathways after acute LPS and epoxomicin administration in mice. Jamart, Cécile; Gomes, Aldrin V.; Dewey, Shannamar; Deldicque, Louise; Raymackers, Jean-Marc; Francaux, Marc // BMC Musculoskeletal Disorders;2014, Vol. 15 Issue 1, p1 

    Background The ubiquitin-proteasome pathway (UPP) is a major protein degradation pathway that is activated during sepsis and has been proposed as a therapeutic target for preventing skeletal muscle loss due to cachexia. Although several studies have investigated the modulation of proteasome...

  • Central role of E3 ubiquitin ligase MG53 in insulin resistance and metabolic disorders. Song, Ruisheng; Peng, Wei; Zhang, Yan; Lv, Fengxiang; Wu, Hong-Kun; Guo, Jiaojiao; Cao, Yongxing; Pi, Yanbin; Zhang, Xin; Jin, Li; Zhang, Mao; Jiang, Peng; Liu, Fenghua; Meng, Shaoshuai; Zhang, Xiuqin; Jiang, Ping; Cao, Chun-Mei; Xiao, Rui-Ping // Nature;2/21/2013, Vol. 494 Issue 7437, p375 

    Insulin resistance is a fundamental pathogenic factor present in various metabolic disorders including obesity and type 2 diabetes. Although skeletal muscle accounts for 70-90% of insulin-stimulated glucose disposal, the mechanism underlying muscle insulin resistance is poorly understood. Here...

  • Urotensin II Inhibits Skeletal Muscle Glucose Transport Signaling Pathways via the NADPH Oxidase Pathway. Wang, Hong-Xia; Wu, Xin-Rui; Yang, Hui; Yin, Chun-Lin; Shi, Li-Jin; Wang, Xue-Jiang // PLoS ONE;Oct2013, Vol. 8 Issue 10, p1 

    Our previous studies have demonstrated that the urotensin (UII) and its receptor are up-regulated in the skeletal muscle of mice with type II diabetes mellitus (T2DM), but the significance of UII in skeletal muscle insulin resistance remains unknown. The purpose of this study was to investigate...

  • Reduction in PTP-1B Protein Levels in Skeletal Muscle by an Alcoholic Extract of Artemisia dracunculus L. Is Phenotype Dependent. Coulter, Ann A.; Agyropoulos, George; Ribnicky, David M.; Xian Zhang; Wang, Zhang Q.; Cefalu, William T. // Diabetes;Jun2007 Supplement 1, Vol. 56, pA331 

    A screening of botanicals revealed that an extract of Artemisia dracunculus L. (Russian tarragon), called PMI-5011, increases insulin sensitivity in diabetic mice. We are currently examining the ability of PMI-5011 to improve insulin sensitivity in subjects with obesity and insulin resistance....

  • Bioavailability Assessment of an Extract of Artemisia dracunculus L with Antidiabetic Activities In Vitro and In Vivo. Ribnicky, David M.; Poulev, Alexander; Kuhn, Peter E.; Logendra, Sithes; Zuberi, Aamir; Cefalu, William T.; Raskin, Ilya // Diabetes;Jun2007 Supplement 1, Vol. 56, pA559 

    Despite the widespread use of botanicals for treatment and prevention of disease, including Type 2 diabetes, there is a paucity of data regarding the plasma bioavailability of active compounds from plant extracts. An extract of Artemisia dracunculus was shown to decrease hyperglycemia and...

  • MG132-mediated inhibition of the ubiquitin-proteasome pathway ameliorates cancer cachexia. Zhang, Liuping; Tang, Hua; Kou, Yao; Li, Rui; Zheng, Yueyong; Wang, Qiang; Zhou, Xiaoyu; Jin, Liangbin // Journal of Cancer Research & Clinical Oncology;Jul2013, Vol. 139 Issue 7, p1105 

    Purpose: To evaluate the effect of proteasome inhibitor MG132 in cancer cachexia and to delineate the molecular mechanism underlying. Methods: We established an experimental cancer cachexia model by subcutaneously implanting colon 26 cells into the armpits of BALB/c mice. Following...

  • Sirt1 enhances skeletal muscle insulin sensitivity in mice during caloric restriction. Schenk, Simon; McCurdy, Carrie E.; Philp, Andrew; Chen, Mark Z.; Holliday, Michael J.; Bandyopadhyay, Gautum K.; Osborn, Olivia; Baar, Keith; Olefsky1, Jerrold M.; Olefsky, Jerrold M // Journal of Clinical Investigation;Nov2011, Vol. 121 Issue 11, p4281 

    Skeletal muscle insulin resistance is a key component of the etiology of type 2 diabetes. Caloric restriction (CR) enhances the sensitivity of skeletal muscle to insulin. However, the molecular signals within skeletal muscle linking CR to improved insulin action remain largely unknown. Recently,...

  • Complete failure of insulin-transmitted signaling, but not obesity-induced insulin resistance, impairs respiratory chain function in muscle. Franko, A.; Kleist-Retzow, J.; Böse, M.; Sanchez-Lasheras, C.; Brodesser, S.; Krut, O.; Kunz, W.; Wiedermann, D.; Hoehn, M.; Stöhr, O.; Moll, L.; Freude, S.; Krone, W.; Schubert, M.; Wiesner, R. // Journal of Molecular Medicine;Oct2012, Vol. 90 Issue 10, p1145 

    The role of mitochondrial dysfunction in the development of insulin resistance and type 2 diabetes remains controversial. In order to specifically define the relationship between insulin receptor (InsR) signaling, insulin resistance, hyperglycemia, hyperlipidemia and mitochondrial function, we...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics