RESUMO
Aim To explore whether alisol B 23-acetate possesses the therapeutic potential for treatment of type 2 diabetes mellitus ( T2DM ). Methods T2DM mouse model was established by combined administration of streptozotocin and nicotinamide. After three weeks of oral administration of rosiglitazone or alisol B 23-acetate, the blood glucose of type 2 diabetic mice was measured. Oral glucose tolerance test(OGTT) was carried out the next day. Rosiglitazone was chosen as positive drug. 2-[N-(7-nitrobenz-2-oxa-l, 3-diazol-4-yl) amino]-2-deoxy-D-glucose (2-NBDG) uptake assay in adipocytes was adopted to test whether alisol B 23-acetate had effect on glucose uptake in cells. 3T3-Ll pre-adipocytes differentiation model was performed to evaluate whether alisol B 23-acetate promoted adipo-genesis. Results Mice exhibited significantly higher blood glucose concentration after intraperitoneal injection of streptozotocin and nicotinamide for three weeks, as examined by blood glucose concentration on day 21 and OGTT on day 22, compared with normal mice in blank control group. After orally administrating alisol B 23-acetate at dose of 5 mg • kg-1 , 10 mg • kg-1 ,20 mg • kg-1 daily for three weeks, respectively, or orally administered rosiglitazone at dose of 10 mg • kg-1 daily for three weeks, blood glucose greatly decreased in type 2 diabetic mice. Moreover, insulin resistance was also improved to a certain degree during OGTT. Furthermore, alisol B 23-acetate not only increased insulin-induced glucose uptake in adipocytes at the concentration of 30 mmol • L-1 glucose, but also accelerated 3T3-L1 pre-adipocytes differentiation process at concentration of 1 μmol • L-1 and 10 μmol • L-1 . Conclusions Alisol B 23-acetate reduces blood glucose of type 2 diabetic mice, promotes pre-adipocyte differentiation and increases glucose uptake in adipocytes; however, the mechanism of action needs further exploration.
RESUMO
Aim To investigate the effect of liraglutide on expression of fibroblast growth factor 21 in white ad-ipose tissues and its mechanisms. Methods Male SD rats were subjected to a standard control diet or high-fat diet ( HFD) for 12 weeks, then the HFD group was in-jected introperitoneally with 30 mg · kg-1 streptozoto-cin to induce type 2 diabetes mellitus model. Half number of rats of type 2 diabetes mellitus were injected with liraglutide ( DM +LRG, 0. 4 mg · kg-1 · d-1 , two times one day ) for another 6 weeks. Serum bio-chemical indices and FGF21 levels were detected. The pathological changes in epididymal adipose tissues were detected by HE staining. The mRNA and protein ex-pression and phosphorylation of FGF21 , peroxisome proliferator-activated receptor γ ( PPARγ) , fibroblast growth factor receptor 3 (FGFR3),β-Klotho, liver ki-nase B1(LKB1), AMP-activated kinase (AMPK), a-cetyl-CoA carboxylase ( ACC ) and phosphorylation of signaling molecules in MAPK pathway were assessed by RT-PCR, immunohistochemistry and Western blot re-spectively. Results Body mass and serum lipid, ALT and AST levels increased in DM group, while FGF21 level decreased, and the volume of adipose cells in ep-ididymal adipose tissues was expanded. Expressions of FGF21, PPARγ, p-FGFR3, β-Klotho, p-LKB1, p-AMPK, p-ACC were down-regulated, while p-ERK, p-JNK and p-p38 expression were all increased. These indices were reverted by liraglutide treatment. Conclu-sion Liraglutide has significant lipid-lowering effect, which maybe related with increased FGF21 expression, activating AMPK pathway and inhibiting MAPK path-way.