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Article

Liraglutide improves cognitive impairment via the AMPK and PI3K/Akt signaling pathways in type 2 diabetic rats

  • Authors:
    • Ying Yang
    • Hui Fang
    • Gang Xu
    • Yanfeng Zhen
    • Yazhong Zhang
    • Jinli Tian
    • Dandan Zhang
    • Guyue Zhang
    • Jing Xu
  • View Affiliations / Copyright

    Affiliations: Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China, Department of Burns and Orthopedics, Tangshan Gongren Hospital, Tangshan, Hebei 063000, P.R. China, Second Department of Endocrinology, Tangshan Gongren Hospital, Tangshan, Hebei 063000, P.R. China
  • Pages: 2449-2457
    |
    Published online on: June 18, 2018
       https://doi.org/10.3892/mmr.2018.9180
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Abstract

Liraglutide is a type of glucagon‑like‑peptide 1 receptor agonist, which has been reported as a novel type of antidiabetic agent with numerous benefits, including cardiovascular and neuroprotective effects. To the best of our knowledge, few studies to date have reported the potential mechanism underlying the neuroprotective effects of liraglutide on rats with type 2 diabetes mellitus (T2DM). The present study aimed to investigate the neuroprotective actions of liraglutide in diabetic rats and to determine the mechanisms underlying these effects. A total of 30 male T2DM Goto‑Kakizaki (GK) rats (age, 32 weeks; weight, 300‑350 g) and 10 male Wistar rats (age, 32 weeks; weight, 300‑350 g) were used in the present study. Wistar rats received vehicle treatment, and GK rats randomly received treatment with vehicle, low dose of liraglutide (75 µg/kg) or high dose of liraglutide (200 µg/kg) for 28 days. Cognitive deficits were evaluated using the Morris water maze test. The expression levels of phosphoinositide 3‑kinase (PI3K), protein kinase B (Akt), phosphorylated (p)‑Akt, AMP‑activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), Beclin‑1, microtubule‑associated protein light chain 3 (LC)‑3 II, caspase‑3, B‑cell lymphoma 2 (Bcl‑2)‑associated X protein and Bcl‑2 were assessed by western blot analysis. The results demonstrated that diabetic GK rats exhibited cognitive dysfunction, whereas treatment with liraglutide alleviated the learning and memory deficits, particularly in the high‑dose liraglutide group. The expression levels of Beclin‑1 and LC‑3 II were decreased in GK rats; however, this decrease was alleviated in the presence of liraglutide. Liraglutide also reversed T2DM model‑induced increases in mTOR, and decreases in p‑AMPK, PI3K and p‑Akt expression, and modulated the expression of apoptosis‑associated proteins. Furthermore, the administration of liraglutide inhibited apoptosis and exerted a protective effect against cognitive deficits via the activation of autophagy. In conclusion, the protective effects of liraglutide may be associated with increased mTOR expression via activation of the AMPK and PI3K/Akt signaling pathways.
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Copy and paste a formatted citation
Spandidos Publications style
Yang Y, Fang H, Xu G, Zhen Y, Zhang Y, Tian J, Zhang D, Zhang G and Xu J: Liraglutide improves cognitive impairment via the AMPK and PI3K/Akt signaling pathways in type 2 diabetic rats. Mol Med Rep 18: 2449-2457, 2018.
APA
Yang, Y., Fang, H., Xu, G., Zhen, Y., Zhang, Y., Tian, J. ... Xu, J. (2018). Liraglutide improves cognitive impairment via the AMPK and PI3K/Akt signaling pathways in type 2 diabetic rats. Molecular Medicine Reports, 18, 2449-2457. https://doi.org/10.3892/mmr.2018.9180
MLA
Yang, Y., Fang, H., Xu, G., Zhen, Y., Zhang, Y., Tian, J., Zhang, D., Zhang, G., Xu, J."Liraglutide improves cognitive impairment via the AMPK and PI3K/Akt signaling pathways in type 2 diabetic rats". Molecular Medicine Reports 18.2 (2018): 2449-2457.
Chicago
Yang, Y., Fang, H., Xu, G., Zhen, Y., Zhang, Y., Tian, J., Zhang, D., Zhang, G., Xu, J."Liraglutide improves cognitive impairment via the AMPK and PI3K/Akt signaling pathways in type 2 diabetic rats". Molecular Medicine Reports 18, no. 2 (2018): 2449-2457. https://doi.org/10.3892/mmr.2018.9180
Copy and paste a formatted citation
x
Spandidos Publications style
Yang Y, Fang H, Xu G, Zhen Y, Zhang Y, Tian J, Zhang D, Zhang G and Xu J: Liraglutide improves cognitive impairment via the AMPK and PI3K/Akt signaling pathways in type 2 diabetic rats. Mol Med Rep 18: 2449-2457, 2018.
APA
Yang, Y., Fang, H., Xu, G., Zhen, Y., Zhang, Y., Tian, J. ... Xu, J. (2018). Liraglutide improves cognitive impairment via the AMPK and PI3K/Akt signaling pathways in type 2 diabetic rats. Molecular Medicine Reports, 18, 2449-2457. https://doi.org/10.3892/mmr.2018.9180
MLA
Yang, Y., Fang, H., Xu, G., Zhen, Y., Zhang, Y., Tian, J., Zhang, D., Zhang, G., Xu, J."Liraglutide improves cognitive impairment via the AMPK and PI3K/Akt signaling pathways in type 2 diabetic rats". Molecular Medicine Reports 18.2 (2018): 2449-2457.
Chicago
Yang, Y., Fang, H., Xu, G., Zhen, Y., Zhang, Y., Tian, J., Zhang, D., Zhang, G., Xu, J."Liraglutide improves cognitive impairment via the AMPK and PI3K/Akt signaling pathways in type 2 diabetic rats". Molecular Medicine Reports 18, no. 2 (2018): 2449-2457. https://doi.org/10.3892/mmr.2018.9180
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