3-Deoxyglucosone induces insulin resistance by impairing insulin signaling in HepG2 cells

Liang,Guoqiang; Wang,Fei; Song,Xiudao; Zhang,Lurong; Qian,Zhen; Jiang,Guorong

doi:10.3892/mmr.2016.5081

3-Deoxyglucosone induces insulin resistance by impairing insulin signaling in HepG2 cells

Authors:
- Guoqiang Liang
- Fei Wang
- Xiudao Song
- Lurong Zhang
- Zhen Qian
- Guorong Jiang
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Affiliations: Basic Research Laboratory, Suzhou Academy of Wumen Chinese Medicine, Suzhou Hospital of Traditional Chinese Medicine, Suzhou, Jiangsu 215003, P.R. China
Published online on: April 4, 2016 https://doi.org/10.3892/mmr.2016.5081
Pages: 4506-4512

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Abstract

3-Deoxyglucosone (3DG), a highly reactive dicarbonyl intermediate generated during glycation, has been confirmed to be markedly elevated in the plasma of patients with diabetes. Our previous study found that there is an association between increasing accumulation of plasma 3DG and impaired glucose regulation in non-diabetic seniors (females, >50 years old; males, >55 years old). It was also found that 3DG led to impaired plasma glucose homeostasis in healthy mice, however, the mechanisms underlying the deleterious effect of 3DG in diabetes remain to be fully elucidated. The present study aimed to investigate the ability of 3DG to cause hepatic insulin resistance in a cell model by assessing glucose uptake and glycogen content. In addition, the molecular signaling events, including the phosphoinositide 3‑kinase (PI3K)/AKT/glucose transporter 2 (GLUT2) and PI3K/AKT/glycogen synthase kinase‑3 (GSK‑3) pathways, which affect hepatic insulin resistance, were further investigated using Western blot analysis. The results showed that 3DG (10‑300 ng/ml) had no significant effect on HepG2 cell viability, however, the viability of the HepG2 cells decreased with exposure to concentrations of 500 and 1,000 ng/ml. Treatment with non‑cytotoxic 3DG concentrations resulted in decreased uptake of glucose and glycogen content with insulin stimulation, but not under basal conditions. The insulin‑induced expression of GLUT2 and p‑GSK‑3 were eliminated by 3DG (80 and 300 ng/ml), in addition to inhibiting the phosphorylation of downstream effectors of the insulin signaling pathway, including insulin receptor substrate 1, PI3K and AKT. In conclusion, the findings of the present study indicated that the addition of exogenous 3DG directly contributed to the induction of insulin resistance by impairing insulin signaling in the HepG2 cells, which suggested that 3DG may be involved in worsening of the diabetic condition.

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