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NO-1886 Ameliorates Glycogen Metabolism in Insulin-Resistant HepG2 Cells by GSK-3β Signalling

NO-1886 Ameliorates Glycogen Metabolism in Insulin-Resistant HepG2 Cells by GSK-3β Signalling

Zong-Bao Wang, Huai-Cai Zeng, Han-Song Wei, Guang-Hui Yi, Jian Yu, Yue-Ting Wang, Ya-Li Zhang, Wei-Dong Yin

J Pharm Pharmacol. 2012 Feb;64(2):293-301.

PMID: 22221106

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP133208932	NO-1886		133208-93-2	Price

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