A GLP‑1 receptor agonist attenuates human islet amyloid polypeptide‑induced autophagy and apoptosis in MIN6 cells

  • Authors:
    • Xiong Chen
    • Tingting Huang
    • Yujuan Shi
    • Luyin Wang
    • Wei Li
    • Feixia Shen
    • Xuemei Gu
  • View Affiliations

  • Published online on: December 11, 2018     https://doi.org/10.3892/mmr.2018.9741
  • Pages: 1365-1371
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Abstract

Type 2 diabetes mellitus (T2DM) is characterized by the dysfunction and loss of pancreatic islet β‑cells, in part due to islet amyloid deposits derived from islet amyloid polypeptide (IAPP). The glucagon‑like peptide‑1 (GLP‑1) receptor agonist exendin‑4 enhances the insulin secretory response by increasing β‑cell mass in T2DM. However, it is unknown whether exendin‑4 protects β‑cells from IAPP‑mediated autophagy and apoptosis. In the present study, reverse transcription‑quantitative polymerase chain reaction, ELISA and western blotting were used to detected the mRNA and protein expression of insulin/hIAPP and other signaling molecules, while the mechanisms underlying these effects were also determined. Exendin‑4 increased the level of insulin secretion, which was greater than that of IAPP, leading to a beneficial IAPP/insulin secretion pattern. In MIN6 cells incubated with 25 mM glucose, exendin‑4 decreased the ratio of light chain 3 (LC3)‑II/I, which was accompanied by an increase in p62 protein. In a hIAPP‑overexpressing MIN6 cell model, exendin‑4 prevented the hIAPP‑induced increase in the LC3II/I ratio and decrease in p62 expression. In addition, exendin‑4 pretreatment reduced hIAPP‑induced activation of cleaved caspase‑3, suggesting that exendin‑4 may protect MIN6 cells against apoptosis. Taken together, the results highlight hIAPP as a critical mediator of β‑cell loss and suggest that the GLP‑1 receptor agonist exendin‑4 may be a potential therapeutic agent for hIAPP‑induced β‑cell damage.
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February-2019
Volume 19 Issue 2

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Chen X, Huang T, Shi Y, Wang L, Li W, Shen F and Gu X: A GLP‑1 receptor agonist attenuates human islet amyloid polypeptide‑induced autophagy and apoptosis in MIN6 cells. Mol Med Rep 19: 1365-1371, 2019
APA
Chen, X., Huang, T., Shi, Y., Wang, L., Li, W., Shen, F., & Gu, X. (2019). A GLP‑1 receptor agonist attenuates human islet amyloid polypeptide‑induced autophagy and apoptosis in MIN6 cells. Molecular Medicine Reports, 19, 1365-1371. https://doi.org/10.3892/mmr.2018.9741
MLA
Chen, X., Huang, T., Shi, Y., Wang, L., Li, W., Shen, F., Gu, X."A GLP‑1 receptor agonist attenuates human islet amyloid polypeptide‑induced autophagy and apoptosis in MIN6 cells". Molecular Medicine Reports 19.2 (2019): 1365-1371.
Chicago
Chen, X., Huang, T., Shi, Y., Wang, L., Li, W., Shen, F., Gu, X."A GLP‑1 receptor agonist attenuates human islet amyloid polypeptide‑induced autophagy and apoptosis in MIN6 cells". Molecular Medicine Reports 19, no. 2 (2019): 1365-1371. https://doi.org/10.3892/mmr.2018.9741