Dihydrosanguinarine Enhances Glucose Uptake in Mouse 3T3-L1 Cells

Recently, more studies have aimed at identifying selective peroxisome proliferator-activated receptor gamma (PPAR gamma) modulators that transactivate the expression of PPAR gamma-dependent genes as partial agonists to improve diabetic symptoms with fewer side effects compared to classic PPAR gamma agonists such as thiazolidinediones. We found that dihydrosanguinarine (DHS) treatment induced preadipocyte differentiation and lipid droplet accumulation in 3T3-L1 cells, but this effect is weaker than that elicited by the full PPAR gamma agonist troglitazone. Furthermore, this effect was reduced by the addition of a PPAR gamma antagonist, indicating the involvement of PPAR gamma signaling. Our results suggest that the stimulatory effects of DHS on adipocyte differentiation and insulin sensitivity are mediated by suppressing adenosine monophosphateactivated protein kinase (AMPK) alpha, upregulating the expression of PPAR. and its target genes (particularly Glut-4 and adiponectin) and reducing PPAR. phosphorylation. DHS significantly enhanced the glucose uptake in 3T3-L1 adipocytes without observable cytotoxicity at the effective concentration (5 mu M) applied.