Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
July 2013 Volume 8 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
July 2013 Volume 8 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Overexpression of mitofusin 2 improves translocation of glucose transporter 4 in skeletal muscle of high‑fat diet‑fed rats through AMP‑activated protein kinase signaling

  • Authors:
    • Dexian Kong
    • Guangyao Song
    • Chao Wang
    • Huijuan Ma
    • Luping Ren
    • Qian Nie
    • Xuemei Zhang
    • Kexin Gan
  • View Affiliations / Copyright

    Affiliations: Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China, Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei 050017, P.R. China
  • Pages: 205-210
    |
    Published online on: May 2, 2013
       https://doi.org/10.3892/mmr.2013.1457
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Mitofusin 2 (Mfn2) is a mitochondrial membrane protein that plays a role in mitochondrial fusion and metabolism in mammalian cells. Previous studies have reported a positive correlation between Mfn2 expression and insulin sensitivity in non‑diabetic and type 2 diabetic subjects. Thus, the aim of the present study was to investigate whether Mfn2 overexpression improves insulin sensitivity of high‑fat diet (HFD) rats and the possible underlying mechanisms. Male SD rats were randomly divided into four groups: negative control; HFD; HFD plus adenoviral vectors; and HFD plus adenoviral vectors encoding Mfn2. Following an 11‑week treatment protocol, the euglycemic‑hyperinsulinemic clamp technique was applied to evaluate insulin sensitivity in rats. The skeletal muscles from rats in each group were analyzed by real‑time PCR and western blot analysis to determine glucose transporter 4 (GLUT4) expression, translocation and relative translocation signaling. Consistent with Mfn2 repression and glucose intolerance, HFD downregulates GLUT4 expression at the mRNA and protein levels, while Mfn2 overexpression activates AMP‑activated protein kinase (AMPK), increases GLUT4 expression and translocation and improves insulin resistance in the skeletal muscles of HFD rats. Results of the present study indicate that Mfn2 overexpression improves insulin sensitivity and may regulate GLUT4 translocation in an AMPK‑dependent manner in the skeletal muscles of HFD rats. This study is likely to provide insight into the unique role of Mfn2 in promoting glucose uptake, leading to modulation of GLUT4 translocation signaling and maintenance of glucose homeostasis in vivo.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Bach D, Naon D, Pich S, et al: Expression of Mfn2, the Charcot-Marie-Tooth neuropathy type 2A gene, in human skeletal muscle: effects of type 2 diabetes, obesity, weight loss and the regulatory role of tumor necrosis factor alpha and interleukin-6. Diabetes. 54:2685–2693. 2005. View Article : Google Scholar

2 

van den Ouweland JM, Lemkes HH, Ruitenbeek W, et al: Mutation in mitochondrial tRNA(Leu)(UUR) gene in a large pedigree with maternally transmitted type II diabetes mellitus and deafness. Nat Genet. 1:368–371. 1992.PubMed/NCBI

3 

Zorzano A, Liesa M and Palacin M: Mitochondrial dynamics as a bridge between mitochondrial dysfunction and insulin resistance. Arch Physiol Biochem. 115:1–12. 2009. View Article : Google Scholar : PubMed/NCBI

4 

Hoeks J and Schrauwen P: Muscle mitochondria and insulin resistance: a human perspective. Trends Endocrinol Metab. 23:444–450. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Bach D, Pich S, Soriano FX, et al: Mitofusin-2 determines mitochondrial network architecture and mitochondrial metabolism. A novel regulatory mechanism altered in obesity. J Biol Chem. 278:17190–17197. 2003. View Article : Google Scholar : PubMed/NCBI

6 

Chen H, Detmer SA, Ewald AJ, Griffin EE, Fraser SE and Chan DC: Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development. J Cell Biol. 160:189–200. 2003. View Article : Google Scholar : PubMed/NCBI

7 

Soriano FX, Liesa M, Bach D, Chan DC, Palacin M and Zorzano A: Evidence for a mitochondrial regulatory pathway defined by peroxisome proliferator-activated receptor-gamma coactivator-1 alpha, estrogen-related receptor-alpha and mitofusin 2. Diabetes. 55:1783–1791. 2006. View Article : Google Scholar

8 

Sebastián D, Hernández-Alvarez MI, Segalés J, et al: Mitofusin 2 (Mfn2) links mitochondrial and endoplasmic reticulum function with insulin signaling and is essential for normal glucose homeostasis. Proc Natl Acad Sci USA. 109:5523–5528. 2012.PubMed/NCBI

9 

Pich S, Bach D, Briones P, et al: The Charcot-Marie-Tooth type 2A gene product, Mfn2, up-regulates fuel oxidation through expression of OXPHOS system. Hum Mol Genet. 14:1405–1415. 2005. View Article : Google Scholar : PubMed/NCBI

10 

McConell GK and Wadley GD: Potential role of nitric oxide in contraction-stimulated glucose uptake and mitochondrial biogenesis in skeletal muscle. Clin Exp Pharmacol Physiol. 35:1488–1492. 2008.PubMed/NCBI

11 

Zhao HL, Liu LZ, Sui Y, et al: Fatty acids inhibit insulin-mediated glucose transport associated with actin remodeling in rat L6 muscle cells. Acta Diabetol. 47:331–339. 2010. View Article : Google Scholar : PubMed/NCBI

12 

Jaiswal N, Yadav PP, Maurya R, Srivastava AK and Tamrakar AK: Karanjin from Pongamia pinnata induces GLUT4 translocation in skeletal muscle cells in a phosphatidylinositol-3-kinase-independent manner. Eur J Pharmacol. 670:22–28. 2011.

13 

Kim JY, Jo KJ, Kim BJ, Baik HW and Lee SK: 17β-estradiol induces an interaction between adenosine monophosphate-activated protein kinase and the insulin signaling pathway in 3T3-L1 adipocytes. Int J Mol Med. 30:979–985. 2012.

14 

Bi Y, Sun WP, Chen X, Li M, Liang H, Cai MY, Zhu YH, He XY, Xu F and Weng JP: Effect of early insulin therapy on nuclear factor kappaB and cytokine gene expressions in the liver and skeletal muscle of high-fat diet, streptozotocin-treated diabetic rats. Acta Diabetol. 45:167–178. 2008. View Article : Google Scholar : PubMed/NCBI

15 

Iglesias MA, Ye JM, Frangioudakis G, et al: AICAR administration causes an apparent enhancement of muscle and liver insulin action in insulin-resistant high-fat-fed rats. Diabetes. 51:2886–2894. 2002. View Article : Google Scholar : PubMed/NCBI

16 

Sato T, Man ZW, Toide K and Asahi Y: Plasma membrane content of insulin-regulated glucose transporter in skeletal muscle of the male Otsuka Long-Evans Tokushima Fatty rat, a model of non-insulin-dependent diabetes mellitus. FEBS Lett. 407:329–332. 1997. View Article : Google Scholar

17 

Wang ZQ, Zhang XH, Yu Y, et al: Bioactives from bitter melon enhance insulin signaling and modulate acyl carnitine content in skeletal muscle in high-fat diet-fed mice. J Nutr Biochem. 22:1064–1073. 2011. View Article : Google Scholar : PubMed/NCBI

18 

Hernández-Alvarez MI, Thabit H, Burns N, et al: Subjects with early-onset type 2 diabetes show defective activation of the skeletal muscle PGC-1{alpha}/Mitofusin-2 regulatory pathway in response to physical activity. Diabetes Care. 33:645–651. 2010.PubMed/NCBI

19 

Mingrone G, Manco M, Calvani M, Castagneto M, Naon D and Zorzano A: Could the low level of expression of the gene encoding skeletal muscle mitofusin-2 account for the metabolic inflexibility of obesity? Diabetologia. 48:2108–2114. 2005. View Article : Google Scholar : PubMed/NCBI

20 

Chen X and Xu Y: Liver-specific reduction of Mfn2 protein by RNAi results in impaired glycometabolism and lipid homeostasis in BALB/c mice. J Huazhong Univ Sci Technolog Med Sci. 29:689–696. 2009. View Article : Google Scholar : PubMed/NCBI

21 

Mingrone G, Rosa G, Di Rocco P, et al: Skeletal muscle triglycerides lowering is associated with net improvement of insulin sensitivity, TNF-alpha reduction and GLUT4 expression enhancement. Int J Obes Relat Metab Disord. 26:1165–1172. 2002. View Article : Google Scholar : PubMed/NCBI

22 

Yu H, Guo Y, Mi L, Wang X, Li L and Gao W: Mitofusin 2 inhibits angiotensin II-induced myocardial hypertrophy. J Cardiovasc Pharmacol Ther. 16:205–211. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Guo YH, Chen K, Gao W, et al: Overexpression of Mitofusin 2 inhibited oxidized low-density lipoprotein induced vascular smooth muscle cell proliferation and reduced atherosclerotic lesion formation in rabbit. Biochem Biophys Res Commun. 363:411–417. 2007. View Article : Google Scholar

24 

Lugus JJ, Ngoh GA, Bachschmid MM and Walsh K: Mitofusins are required for angiogenic function and modulate different signaling pathways in cultured endothelial cells. J Mol Cell Cardiol. 51:885–893. 2011. View Article : Google Scholar : PubMed/NCBI

25 

Wan-Xin T, Tian-Lei C, Ben W, Wei-Hua W and Ping F: Effect of mitofusin 2 overexpression on the proliferation and apoptosis of high-glucose-induced rat glomerular mesangial cells. J Nephrol. 25:1023–1030. 2012. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Kong D, Song G, Wang C, Ma H, Ren L, Nie Q, Zhang X and Gan K: Overexpression of mitofusin 2 improves translocation of glucose transporter 4 in skeletal muscle of high‑fat diet‑fed rats through AMP‑activated protein kinase signaling. Mol Med Rep 8: 205-210, 2013.
APA
Kong, D., Song, G., Wang, C., Ma, H., Ren, L., Nie, Q. ... Gan, K. (2013). Overexpression of mitofusin 2 improves translocation of glucose transporter 4 in skeletal muscle of high‑fat diet‑fed rats through AMP‑activated protein kinase signaling. Molecular Medicine Reports, 8, 205-210. https://doi.org/10.3892/mmr.2013.1457
MLA
Kong, D., Song, G., Wang, C., Ma, H., Ren, L., Nie, Q., Zhang, X., Gan, K."Overexpression of mitofusin 2 improves translocation of glucose transporter 4 in skeletal muscle of high‑fat diet‑fed rats through AMP‑activated protein kinase signaling". Molecular Medicine Reports 8.1 (2013): 205-210.
Chicago
Kong, D., Song, G., Wang, C., Ma, H., Ren, L., Nie, Q., Zhang, X., Gan, K."Overexpression of mitofusin 2 improves translocation of glucose transporter 4 in skeletal muscle of high‑fat diet‑fed rats through AMP‑activated protein kinase signaling". Molecular Medicine Reports 8, no. 1 (2013): 205-210. https://doi.org/10.3892/mmr.2013.1457
Copy and paste a formatted citation
x
Spandidos Publications style
Kong D, Song G, Wang C, Ma H, Ren L, Nie Q, Zhang X and Gan K: Overexpression of mitofusin 2 improves translocation of glucose transporter 4 in skeletal muscle of high‑fat diet‑fed rats through AMP‑activated protein kinase signaling. Mol Med Rep 8: 205-210, 2013.
APA
Kong, D., Song, G., Wang, C., Ma, H., Ren, L., Nie, Q. ... Gan, K. (2013). Overexpression of mitofusin 2 improves translocation of glucose transporter 4 in skeletal muscle of high‑fat diet‑fed rats through AMP‑activated protein kinase signaling. Molecular Medicine Reports, 8, 205-210. https://doi.org/10.3892/mmr.2013.1457
MLA
Kong, D., Song, G., Wang, C., Ma, H., Ren, L., Nie, Q., Zhang, X., Gan, K."Overexpression of mitofusin 2 improves translocation of glucose transporter 4 in skeletal muscle of high‑fat diet‑fed rats through AMP‑activated protein kinase signaling". Molecular Medicine Reports 8.1 (2013): 205-210.
Chicago
Kong, D., Song, G., Wang, C., Ma, H., Ren, L., Nie, Q., Zhang, X., Gan, K."Overexpression of mitofusin 2 improves translocation of glucose transporter 4 in skeletal muscle of high‑fat diet‑fed rats through AMP‑activated protein kinase signaling". Molecular Medicine Reports 8, no. 1 (2013): 205-210. https://doi.org/10.3892/mmr.2013.1457
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team