Open AccessA GLP‑1 receptor agonist attenuates human islet amyloid polypeptide‑induced autophagy and apoptosis in MIN6 cells
Author(s) -
Xiong Chen,
Tingting Huang,
Yujuan Shi,
Luyin Wang,
Wei Li,
Feixia Shen,
Xin Gu
Publication year - 2018
Publication title -
molecular medicine reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.727
H-Index - 56
eISSN - 1791-3004
pISSN - 1791-2997
DOI - 10.3892/mmr.2018.9741
Subject(s) - islet , agonist , autophagy , apoptosis , endocrinology , amylin , medicine , amyloid (mycology) , receptor , downregulation and upregulation , cell , chemistry , insulin , microbiology and biotechnology , biology , biochemistry , inorganic chemistry , gene
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.