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Published on: May 16, 2021
NO-1886 ameliorates glycogen metabolism in insulin-resistant HepG2 cells by GSK-3β signalling
Zong-Bao Wang1, Huai-Cai Zeng, Han-Song Wei
1Key Laboratory for Arteriosclerology of Hunan Province, University of South China, Hengyang, Hunan, China.
Objectives:
The aim of the study was to elucidate the possible role and mechanism of NO-1886 (ibrolipim, a lipoprotein lipase activator) in ameliorating insulin resistance induced by high palmitate.
Methods:
HepG2 cells were cultured in RPMI 1640 medium and were treated with palmitate to induce insulin resistance. Free fatty acids (FFAs), glucose, glycogen, cell viability and mRNA and protein levels were analysed separately.
Key Findings:
We found that HepG2 cells treated with 0.5 mm palmitate for 48 h led to a significant decrease of insulin-induced glucose consumption (from 2.89 ± 0.85 mm in the control to 0.57 ± 0.44 mm in palmitate). Insulin resistance (IR) of HepG2 cells was induced by 0.5 mm palmitate for 48 h. NO-1886 stimulated glucose consumption, glycogen synthesis and FFA absorption in insulin-resistant HepG2 cells. Maximum stimulation effects were observed with 10 µm NO-1886 for 24 h. Compared with the dimethyl sulfoxide-treated group, 2.5 µm NO-1886 or higher could induce the mRNA expression of lipoprotein lipase. Meanwhile, NO-1886 increased the protein content of P-GSK-3βser(9) and decreased the protein level of GSK-3β in insulin-resistant HepG2 cells, but NO-1886 didn't change the protein levels of PI3-Kp85 and Akt2.
Conclusion:
Lipoprotein lipase activator NO-1886 could increase glycogen synthesis in HepG2 cells and could ameliorate the insulin resistance, which was associated with GSK-3 signalling.
Insights
NO-1886, a lipoprotein lipase activator, effectively combats palmitate-induced insulin resistance in HepG2 cells. It enhances glucose consumption and glycogen synthesis, potentially through GSK-3 signaling pathways.
Area of Science:
- Biochemistry
- Cell Biology
- Metabolic Research
Background:
- Insulin resistance is a key metabolic disorder.
- Palmitate exposure in HepG2 cells mimics insulin resistance.
- Understanding novel therapeutic mechanisms is crucial.
Purpose of the Study:
- To investigate NO-1886's role in palmitate-induced insulin resistance.
- To elucidate the molecular mechanisms of NO-1886 action.
Main Methods:
- HepG2 cells were treated with palmitate to induce insulin resistance.
- NO-1886's effects on glucose, glycogen, and free fatty acids were analyzed.
- mRNA and protein levels of key signaling molecules were assessed.
Main Results:
- Palmitate significantly reduced insulin-induced glucose consumption.
- NO-1886 (10 µM) stimulated glucose consumption, glycogen synthesis, and FFA absorption.
- NO-1886 upregulated lipoprotein lipase mRNA and modulated GSK-3β phosphorylation.
Conclusions:
- NO-1886 ameliorates insulin resistance in HepG2 cells.
- Glycogen synthesis is enhanced by NO-1886.
- The mechanism involves GSK-3 signaling pathways.
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