Molecules · 2018 · 74 citations · 16 references
Life SciencesBiochemistryEndocrinologyCell SignalingMetabolic RegulationSignal TransductionAdipose TissueDiabetes MellitusInsulin ResistanceLipid MetabolismMetabolic SignalingPolysaccharide FunctionAdipocyte Insulin SignalingAntidiabetic ActivityFatty Acid BindingInsulin Sensitivity AdaptationInsulin SignalingInsulin Signaling PathwayIntracellular Lipid AccumulationLipid Accumulation
Astragalus polysaccharide (APS) is an important bioactive component of Astragalus membranaceus which is used as an anti-diabetes herb in traditional Chinese medicine. The objective of this study was to investigate the effects and mechanisms of APS on insulin-sensitizing of adipocytes. Mouse 3T3-L1 preadipocytes were used as a model. The results showed that APS increased preadipocytes proliferation in a dose dependent manner, and 0.1 μg/mL APS sufficiently increased Proliferating Cell Nuclear Antigen (PCNA) content (p < 0.01). Moreover, APS enhanced intracellular lipid accumulation and mRNA expression of proliferator-activated receptor γ (PPARγ, p < 0.01), CCAAT/enhancer binding protein α (C/EBPα, p < 0.01) and fatty acid binding protein (aP2, p < 0.01). As expected, corresponding protein contents were elevated. Importantly, APS increased 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino)-2-Deoxyglucose (2-NBDG) uptake (p < 0.01). Meanwhile, both mRNA and protein content of glucose transporter 4 (Glut4) were elevated by APS (p < 0.01). The APS treatment enhanced tyrosine phosphorylation of insulin receptor substrate 1 (IRS1, p < 0.05) and phosphor-Akt content (p < 0.01). Besides, phosphorylated AMP-activated protein kinase (AMPK) content was increased in the APS treated cells (p < 0.01). Taken together, APS improved insulin sensitivity by enhancing glucose uptake, possibly through AMPK activation. These results suggested that APS might be a therapeutic candidate for insulin resistance.
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Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver
E. Dale Abel, Odile D. Peroni, Jason K. Kim et al. · Nature · 2001 · 1.3K citations