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A diterpene derivative enhanced insulin signaling induced by high glucose level in HepG2 cells
Peilei Hou1, Yanbo Qu2, Zhixin Liao3
1Department of Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Southeast University, Nanjing, People's Republic of China.
Abstract:
The predominant feature of type 2 diabetes is insulin resistance. Identifying a drug able to reduce insulin resistance is an urgent requirement. ent-3α-Formylabieta-8(14),13(15)-dien-16,12β-olide had been identified as a new diterpene derivative which showed anticancer activity. This study explores the hypoglycemic effect of ent-3α-formylabieta-8(14),13(15)-dien-16,12β-olide and studied its mechanism. The insulin response of HepG2 cells following ent-3α-formylabieta-8(14),13(15)-dien-16,12β-olide treatment, as a model for liver cancer cells, was assessed. The results demonstrated that hyperglycemia resulted in a significant increase in the levels of insulin receptor substrate-1 (IRS-1) serine phosphorylation and decrease in Akt phosphorylation. High glucose also inhibited the phosphorylation of insulin-dependent GSK3β. ent-3α-Formylabieta-8(14),13(15)-dien-16,12β-olide treatment improved the effect of insulin on the phosphorylation of IRS-1 Ser307. In addition, this study demonstrated that the effect of ent-3α-formylabieta-8(14),13(15)-dien-16,12β-olide was dependent on the activation of AMP-activated protein kinase. Collectively, experimental data indicated an association between insulin resistance and hyperglycemia in HepG2 cells, and that ent-3α-formylabieta-8(14),13(15)-dien-16,12β-olide reduces IRS-1 Ser307 phosphorylation via activating AMPK, thereby decreasing the insulin signaling blockade.
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