Liraglutide ameliorates glycometabolism and insulin resistance through the upregulation of GLUT4 in diabetic KKAy mice

  • Authors:
    • Li-Na Chen
    • Juan Lyu
    • Xue-Fei Yang
    • Wen-Jun Ji
    • Bing-Xiang Yuan
    • Ming-Xia Chen
    • Xin Ma
    • Bing Wang
  • View Affiliations

  • Published online on: July 19, 2013     https://doi.org/10.3892/ijmm.2013.1453
  • Pages: 892-900
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Abstract

Liraglutide, a long-lasting glucagon‑like peptide‑1 analogue, has been used for the treatment of patients with type 2 diabetes mellitus since 2009. In this study, we investigated the anti-diabetic effects and mechanisms of action of liraglutide in a spontaneous diabetic animal model, using KK/Upj-Ay/J (KKAy) mice. The KKAy mice were divided into 2 groups, the liraglutide group (mice were treated with 250 µg/kg/day liraglutide) and the model group (treated with an equivalent amount of normal saline). C57BL/6J mice were used as the controls (treated with an equivalent amount of normal saline). The treatment period lasted 6 weeks. During this treatment period, fasting blood glucose (FBG) levels and the body weight of the mice were measured on a weekly basis. Our results revealed that liraglutide significantly decreased FBG levels, the area under the curve following a oral glucose tolerance test and insulin tolerance test, increased serum insulin levels, reduced homeostasis model assessment of insulin resistance and increased the insulin sensitivity index. Furthermore, liraglutide ameliorated glycometabolism dysfunction by increasing glycolysis via hexokinase and glycogenesis via pyruvate kinase activation. An ultrastructural examination of the pancreas revealed that liraglutide improved the damaged state of islet β cells and increased the number of insulin secretory granules. The real-time PCR results revealed that the gene expression of glucose transporter 4 (GLUT4) increased following treatment with liraglutide. Liraglutide also upregulated the protein expression of GLUT4 in liver tissue and skeletal muscle. Our results suggest that liraglutide ameliorates glycometabolism and insulin resistance in diabetic KKAy mice by stimulating insulin secretion, increasing glycogenesis and glycolysis and upregulating the expression of GLUT4.
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October 2013
Volume 32 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Chen L, Lyu J, Yang X, Ji W, Yuan B, Chen M, Ma X and Wang B: Liraglutide ameliorates glycometabolism and insulin resistance through the upregulation of GLUT4 in diabetic KKAy mice. Int J Mol Med 32: 892-900, 2013
APA
Chen, L., Lyu, J., Yang, X., Ji, W., Yuan, B., Chen, M. ... Wang, B. (2013). Liraglutide ameliorates glycometabolism and insulin resistance through the upregulation of GLUT4 in diabetic KKAy mice. International Journal of Molecular Medicine, 32, 892-900. https://doi.org/10.3892/ijmm.2013.1453
MLA
Chen, L., Lyu, J., Yang, X., Ji, W., Yuan, B., Chen, M., Ma, X., Wang, B."Liraglutide ameliorates glycometabolism and insulin resistance through the upregulation of GLUT4 in diabetic KKAy mice". International Journal of Molecular Medicine 32.4 (2013): 892-900.
Chicago
Chen, L., Lyu, J., Yang, X., Ji, W., Yuan, B., Chen, M., Ma, X., Wang, B."Liraglutide ameliorates glycometabolism and insulin resistance through the upregulation of GLUT4 in diabetic KKAy mice". International Journal of Molecular Medicine 32, no. 4 (2013): 892-900. https://doi.org/10.3892/ijmm.2013.1453