MicroRNA‑152 regulates insulin secretion and pancreatic β cell proliferation by targeting PI3Kα

Chen,Li; Qian,Haiyun; Xue,Junli; Zhang,Juan; Chen,Hao

doi:10.3892/mmr.2018.9359

MicroRNA‑152 regulates insulin secretion and pancreatic β cell proliferation by targeting PI3Kα

Authors:
- Li Chen
- Haiyun Qian
- Junli Xue
- Juan Zhang
- Hao Chen
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Affiliations: Department of Endocrinology, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jingzhou, Hubei 434020, P.R. China, Department of Cardiothoracic Surgery, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jingzhou, Hubei 434020, P.R. China
Published online on: August 8, 2018 https://doi.org/10.3892/mmr.2018.9359
Pages: 4113-4121

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Abstract

An increasing number of microRNAs (miRNAs/miRs) are reported to have important roles in diabetes. Glucose‑stimulated insulin secretion and pancreatic β cell proliferation are essential in the control of metabolic disorder, however, the underlying molecular mechanisms remain unclear. The present study investigated the function of miR‑152 in diabetes. The results of reverse transcription‑quantitative polymerase chain reaction demonstrated that miR‑152 levels in the blood were markedly reduced in patients with diabetes compared with nondiabetic controls. In addition, a high blood glucose concentration was significantly associated with reduced miR‑152 expression. Furthermore, overexpression of miR‑152 using miR‑152 mimics promoted the proliferation of INS‑1 and MIN6 cells, as determined by an MTT assay, in addition to insulin secretion, while knockdown of miR‑152 using an inhibitor led to the opposite effects. Phosphatidylinositol 3‑kinase (PI3K) signaling has been reported to inhibit insulin secretion, however, the regulation of PI3K in the pancreatic β cell is poorly understood. The present study identified that PI3K catalytic subunit α (PI3Kα) was a direct target gene of miR‑152 using a luciferase reporter assay, and miR‑152 inhibited the expression of PI3Kα at the protein level, which was determined by western blotting. Therefore, the regulation of insulin secretion and pancreatic β cell proliferation may occur via the miR‑152/PI3Kα axis. The overexpression of PI3Kα in INS‑1 and MIN6 cells partially reduced the effects of miR‑152 overexpression on insulin secretion. Consistently, PI3Kα levels were reduced in murine pancreatic islets following treatment with 20 mM glucose, and increased in blood samples from patients with diabetes compared with healthy individuals. In conclusion, the results of the present study demonstrate that miR‑152 may have an important role in pancreatic β cell function, and established an association between miR‑152 and the PI3Kα axis. Therefore, targeting PI3Kα may be a potential therapeutic option for diabetes.

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