NO-1886 ameliorates glycogen metabolism in insulin-resistant HepG2 cells by GSK-3β signalling.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Key Laboratory for Arteriosclerology of Hunan Province, University of South China, Hengyang, Hunan, China.
Zong-Bao
ZB
Wang
Huai-Cai
HC
Zeng
Han-Song
HS
Wei
Guang-Hui
GH
Yi
Jian
J
Yu
Yue-Ting
YT
Wang
Ya-Li
YL
Zhang
Wei-Dong
WD
Yin
D001549:Benzamides / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D050261:Glycogenolysis / Q000187:drug effects*; D056945:Hep G2 Cells; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D058867:Lipoprotein Lipase Activators / Q000737:chemistry / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000494:pharmacology*; D010168:Palmitates / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013223:Statistics as Topic
D001549:Benzamides; D058867:Lipoprotein Lipase Activators; D009943:Organophosphorus Compounds; D010168:Palmitates; C082137:4-diethoxyphosphorylmethyl-N-(4-bromo-2-cyanophenyl)benzamide; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3