Geniposide promotes autophagy to inhibit insulin resistance in HepG2 cells via P62/NF‑κB/GLUT‑4

Jiang,Hongwei; Ma,Yujin; Yan,Junqiang; Liu,Jie; Li,Liping

doi:10.3892/mmr.2017.7503

Geniposide promotes autophagy to inhibit insulin resistance in HepG2 cells via P62/NF‑κB/GLUT‑4

Authors:
- Hongwei Jiang
- Yujin Ma
- Junqiang Yan
- Jie Liu
- Liping Li
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Affiliations: Department of Endocrinology, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China, Department of Neurology, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China
Published online on: September 18, 2017 https://doi.org/10.3892/mmr.2017.7503
Pages: 7237-7244
Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Insulin resistance (IR) is known to be an important factor, which can lead to the onset of type 2 diabetes. Autophagy is a cellular process, which sequesters senescent or damaged proteins in autophagosomes for recycling of their products. Insulin and intracellular molecules, including mammalian target of rapamycin (mTOR), are well‑known inhibitors of autophagy. In patients with type 2 diabetes, the expression levels of glucose transporter 4 (GLUT‑4) in skeletal muscles are significantly decreased, indicating decreased glucose‑processing ability. Geniposide is an iridoid compound isolated from Gardenia jasminoides Ellis. Previously, it was reported that geniposide significantly promoted glucose uptake. In the present study, a HepG2 cell model of IR was constructed to determine whether geniposide can promote autophagy to inhibit insulin resistance in HepG2 cells via P62/nuclear factor (NF)‑κB/GLUT‑4. Cell proliferation was analyzed by performing an MTT assay, and the mRNA expression levels of NF‑κB and GLUT‑4 were assessed using semi‑quantitative polymerase chain reaction and immunohistochemical staining. In addition, the protein levels of GLUT‑4, P62 and phosphorylated‑P65 were assessed by western blotting. The expression of GLUT‑4 was initially increased following geniposide treatment, decreasing in time to its lowest level at 8 h. The expression levels of NF‑κB and GLUT‑4 in the IR cells treated with and without geniposide were significantly different, compared with those in the control group. Geniposide promoted autophagy in the IR HepG2 cells and significantly improved IR in the HepG2 cells, which may be associated with the dynamic regulation of the P62/NF‑κB/GLUT‑4 pathway.

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