【Animal modeling】-Effect of curcumin on glucose transport and PI3K/Akt signaling pathway in adipocytes of type 2 diabetic rats

  Objective: To investigate the effect of curcumin on glucose transport and phosphatidylinositol kinase-3 (PI3K)/protein kinase B (Akt) signaling pathway in adipocytes of type 2 diabetes mellitus (T2DM) rats.

  Methods: 90 SD rats were randomly divided into normal group, model group (high-fat feeding), curcumin low-dose group (50 mg/kg), curcumin medium-dose group (150 mg/kg), curcumin high-dose group ( 250mg/kg) and rosiglitazone group (1.35mg/kg), 15 rats in each group. The body weight of the rats was measured immediately after administration, 2 weeks after administration, and 8 weeks after administration, and blood was collected by fasting for 12 hours at the 8th week after administration , respectively detected fasting blood glucose (FBG), fasting insulin (FINS) expression, calculated insulin resistance index (HOMA-IR), triglyceride (TG), low/high density lipoprotein cholesterol (LDC-C/HDL-C), Total cholesterol (TC) expression. Glucose perfusion rate was determined by positive sugar clamp assay, translocation of glucose transporter 4 (GluT4) in adipocyte membrane was detected by fluorescence immunoassay, GluT4 in adipocytes was detected by real-time quantitative PCR (qRT-PCR), and protein immunoassay was performed. The expression of GluT4, p-PI3K, insulin receptor substrate 2 (Irs2) and p-Akt in adipocytes was detected by blotting.

  Results: Compared with the normal group, the body weight of the model group increased immediately after administration, 2 weeks after administration, and decreased after 8 weeks of administration; compared with the model group, curcumin was administered immediately, 2 weeks, and 8 weeks after administration. The body weight of the treatment group and rosiglitazone group decreased (P<0.05). Compared with the normal group, FBG, FINS, HOMA-IR, HDC-L, LDC-L, TC, and TG in the model group all increased, and the glucose The glucose injection rate decreased in a dose-dependent manner; the GluT4 mRNA was increased in the model group, and the protein expressions of GluT4, Irs2, p-PI3K/PI3K, pAkt/Akt were significantly decreased in the model group; the above differences were statistically significant (P<0.05). Compared with the curcumin treatment group and the rosiglitazone group, the levels of FBG, FINS, HOMA-IR, HDC-L, LDC-L, TC and TG were significantly decreased; the glucose injection rate was significantly increased; The protein expression of Irs2,p-PI3K/PI3K,pAkt/Akt was significantly increased; the above differences were all statistically significant (P<0.05), and the difference between the three curcumin dose groups was also statistically significant (P<0.05) .

  Conclusion: Curcumin can improve the insulin sensitivity of T2DM rats, which may be achieved by activating the PI3K/Akt signaling pathway to promote the transport of GluT4 membrane in adipocytes, increase the uptake of glucose by adipocytes, and then relieve the balance of blood glucose metabolism.