Agents that stimulate
glucose uptake and improve
insulin resistance may be useful in the management of
type 2 diabetes mellitus (DM). Thus, the aims of this study were to assess the effects of
aromadendrin, a
flavonoid from Gleditsia sinensis
Lam., on stimulation of
glucose uptake and improvement of
insulin resistance and to characterize the molecular mechanisms underlying these activities.
Insulin-stimulated
glucose uptake was measured in HepG2 cells and in differentiated 3T3-L1 adipocytes using 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-
2-deoxy-D-glucose (2-NBDG), a fluorescent
D-glucose analog. Expression of the peroxisome proliferator-activated receptor-γ2 (PPARγ2) and
adipocyte-specific fatty acid binding protein (aP2) mRNAs and the PPARγ2
protein was analyzed in adipocytes using RT-PCR and immunoblotting, respectively.
Insulin-stimulated
protein kinase B (Akt/PKB) phosphorylation was measured in high
glucose-induced,
insulin-resistant HepG2 cells. Similar to 30 μmol/l
rosiglitazone, treatment with 30 μmol/l
aromadendrin significantly stimulated
insulin-sensitive
glucose uptake in both HepG2 cells and 3T3-L1 adipocytes.
Aromadendrin treatment also enhanced adipogenesis and caused increases in the expression of PPARγ2 and aP2 mRNAs and the PPARγ2
protein in differentiated 3T3-L1 adipocytes. In high
glucose-induced,
insulin-resistant HepG2 cells,
aromadendrin reversed the inhibition of Akt/PKB phosphorylation in response to
insulin, which could be abrogated by pretreatment with
LY294002, a
phosphatidylinositol 3-kinase (PI3K) inhibitor.
Aromadendrin treatment induced adipogenesis by increases in PPARγ2 expression, resulting in stimulation of
glucose uptake and ameliorated
insulin resistance. These findings suggest that
aromadendrin may represent a potential therapeutic candidate for the management of type 2 DM.