Fig. 3.
Inhibition of G6PC/G6pc expression by NPC43 in both human HepG2 and mouse AML-12 liver cells as well as in the liver of Leprdb/db mice. a Insulin-mimetic activity of NPC43 in the inhibition of G6PC expression in human HepG2 cells. HepG2 cells were treated without (control) or with indicated concentrations of insulin or NPC43 in serum-free media for 40 h and then subjected to QRT-PCR analysis. Mean ± SD of four replicates per group and P value (vs. control) was determined by performing Student’s t test. b Insulin-mimetic activity of NPC43 in the inhibition of G6pc expression, and the cooperative action of both NPC43 and insulin in the inhibition of G6pc expression in mouse AML-12 cells. AML-12 cells were pretreated without or with NPC43 (1.9 or 3.8 μM) in FBS-containing but ITS/Dex-free media for 24 h. Then these AML-12 cells were treated without or with insulin (10 or 100 nM), NPC43 (1.9 or 3.8 μM) or both in serum/ITS/Dex-free media for 6 h, and subjected to QRT-PCR analysis. Data were obtained from two combined experiments and presented as mean ± SD of the indicated number (shown inside the column in the bar graph) of samples or replicates per group. *P < 0.05, **P < 0.01, ***P < 0.001 vs. non-insulin/NPC43 group (Student’s t test). Statistical results (Student’s t test) between NPC43-treated and both NPC43 and insulin-treated groups were also shown in the bar graph. c Reduced G6pc mRNA in the livers of Leprdb/db mice after chronic oral administration of NPC43. Leprdb/db mice at postnatal day 65 were fed (by oral gavage) with 0.5% CMC or NPC43 (dissolved in 0.5% CMC, 1.08 and 5.4 mg/kg BW) daily for 9 days. Liver tissues from 0.5% CMC- or NPC43-treated Leprdb/db mice were collected and subjected to QRT-PCR analysis. Mean ± SEM. P values (vs. the 0.5% CMC group, Student’s t test). d Reduced G6pc mRNA in the livers of Leprdb/db mice after chronic i.p. treatment with NPC43. Leprdb/db mice at postnatal day 38 were i.p. injected with 0.2% DMSO/saline (v/v) or NPC43 (0.136 mg/kg BW) daily for 52 days. Liver tissues from these DMSO/saline- or NPC43-treated Leprdb/db mice were collected and subjected to QRT-PCR analysis. Mean ± SEM. P value vs. the DMSO/saline group (Student’s t test)