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Article

Glucagon-like peptide 1 receptor agonist ameliorates the insulin resistance function of islet β cells via the activation of PDX-1/JAK signaling transduction in C57/BL6 mice with high-fat diet-induced diabetes

  • Authors:
    • Tao Hao
    • Hongtao Zhang
    • Sheyu Li
    • Haoming Tian
  • View Affiliations / Copyright

    Affiliations: Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China
  • Pages: 1029-1036
    |
    Published online on: March 7, 2017
       https://doi.org/10.3892/ijmm.2017.2910
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Abstract

Long-term exposure to a high-fat diet (HFD) causes glucotoxicity and lipotoxicity in islet β cells and leads to the development of metabolic dysfunctions. Reductions in pancreatic and duodenal homeobox-1 (PDX-1) expression have been shown to induce type 2 diabetes mellitus by causing impairments to islet β cells. Glucagon-like peptide 1 (GLP-1) treatment reduces endogenous insulin resistance in HFD-induced type 2 diabetes mellitus. In the present study, the underlying mechanism by which GLP-1 exerts its function in type 2 diabetes mellitus was investigated. The effect of liraglutide (GLP-1 receptor agonist) administration on glucose tolerance, insulin release, and glucose-dependent insulinotropic polypeptide level was detected in a HFD-induced diabetes C57/BL6 mouse model. Moreover, the role of liraglutide administration on the activity of PDX-1 was quantified to demonstrate the association between the two indicators. The results showed that administration of liraglutide could ameliorate the impairments to β cells due to HFD consumption. Liraglutide restored the insulin capacity and stimulated glucose disposal by improving the function and increasing the number of islet β cells. Furthermore, the hyperplasia and redundant function of islet α cells were inhibited by liraglutide treatment as well. At the molecular level, administration of liraglutide induced the expression of PDX-1, MafA, p-JAK2 and p-Stat3 in HFD model to relatively normal levels. It was suggested that the effect of liraglutide-induced activation of GLP-1 was exerted via activation of PDX-1 rather than its function in decreasing body weight. The study demonstrated that GLP-1 played an essential role in type 2 diabetes mellitus.
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Copy and paste a formatted citation
Spandidos Publications style
Hao T, Zhang H, Li S and Tian H: Glucagon-like peptide 1 receptor agonist ameliorates the insulin resistance function of islet β cells via the activation of PDX-1/JAK signaling transduction in C57/BL6 mice with high-fat diet-induced diabetes. Int J Mol Med 39: 1029-1036, 2017.
APA
Hao, T., Zhang, H., Li, S., & Tian, H. (2017). Glucagon-like peptide 1 receptor agonist ameliorates the insulin resistance function of islet β cells via the activation of PDX-1/JAK signaling transduction in C57/BL6 mice with high-fat diet-induced diabetes. International Journal of Molecular Medicine, 39, 1029-1036. https://doi.org/10.3892/ijmm.2017.2910
MLA
Hao, T., Zhang, H., Li, S., Tian, H."Glucagon-like peptide 1 receptor agonist ameliorates the insulin resistance function of islet β cells via the activation of PDX-1/JAK signaling transduction in C57/BL6 mice with high-fat diet-induced diabetes". International Journal of Molecular Medicine 39.4 (2017): 1029-1036.
Chicago
Hao, T., Zhang, H., Li, S., Tian, H."Glucagon-like peptide 1 receptor agonist ameliorates the insulin resistance function of islet β cells via the activation of PDX-1/JAK signaling transduction in C57/BL6 mice with high-fat diet-induced diabetes". International Journal of Molecular Medicine 39, no. 4 (2017): 1029-1036. https://doi.org/10.3892/ijmm.2017.2910
Copy and paste a formatted citation
x
Spandidos Publications style
Hao T, Zhang H, Li S and Tian H: Glucagon-like peptide 1 receptor agonist ameliorates the insulin resistance function of islet β cells via the activation of PDX-1/JAK signaling transduction in C57/BL6 mice with high-fat diet-induced diabetes. Int J Mol Med 39: 1029-1036, 2017.
APA
Hao, T., Zhang, H., Li, S., & Tian, H. (2017). Glucagon-like peptide 1 receptor agonist ameliorates the insulin resistance function of islet β cells via the activation of PDX-1/JAK signaling transduction in C57/BL6 mice with high-fat diet-induced diabetes. International Journal of Molecular Medicine, 39, 1029-1036. https://doi.org/10.3892/ijmm.2017.2910
MLA
Hao, T., Zhang, H., Li, S., Tian, H."Glucagon-like peptide 1 receptor agonist ameliorates the insulin resistance function of islet β cells via the activation of PDX-1/JAK signaling transduction in C57/BL6 mice with high-fat diet-induced diabetes". International Journal of Molecular Medicine 39.4 (2017): 1029-1036.
Chicago
Hao, T., Zhang, H., Li, S., Tian, H."Glucagon-like peptide 1 receptor agonist ameliorates the insulin resistance function of islet β cells via the activation of PDX-1/JAK signaling transduction in C57/BL6 mice with high-fat diet-induced diabetes". International Journal of Molecular Medicine 39, no. 4 (2017): 1029-1036. https://doi.org/10.3892/ijmm.2017.2910
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