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Objective:To investigate the effects and mechanisms of curcumin on insulin resistance in streptozocin-induced diabetic rats.Methods:Diabetic rats were induced by intraperitoneal injection of STZ, then all the rats were randomly divided into diabetes (DM), diabetes+ curcumin (DM+ Cur), and diabetes + buffer control (DM+ NC) groups. Normal SD rats were used as control group (NC). The DM+ Cur group was treated with curcumin, while the DM+ NC group was treated with equal-volume buffer. The test lasted 12 weeks. The blood glucose was detected, and hyperinsulinemic-euglycemic clamp test was performed to estimate peripheral insulin resistance. At the end of the experiments, rats were killed and the total protein and cell membrane protein were extracted from skeletal muscle. The levels of phosphorylated PI3K, phosphorylated AKT, total PI3K, and total AKT were measured by Western blot. The levels of total GLUT4 and GLUT4 of cell membrane were also detected by Western blot, GLUT4 levels in skeletal muscle cell membranes were detected by immunofluorescence.Results:Blood glucose levels of DM+ Cur group were lower than those of DM group [(18.67±1.99 vs 24.38±2.88) mmol/L, P<0.05], and insulin resistance was also improved[the average GIR(14.69±0.29 vs 10.25±0.30) mg·kg -1·min -1, P<0.01]. The phosphorylation levels of PI3K and AKT were increased, and GLUT4 translocation to the cell membrane was increased. Conclusion:By activating the PI3K/AKT pathway, curcumin promotes GLUT4 translocation, increases skeletal muscle glucose uptake, and finally improves insulin resistance.
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Objective:To investigate the changes of proopiomelanocortin(POMC) expression in hypothalamus and corresponding metabolism in miR-21 knockout mice.Methods:miR-21 knockout or wild-type C57BL/6J mice were divided into diabetic group and control group, respectively. Diabetic mice model were forged with high-fat diet and low-dose streptozotocin. The changes of body weight and blood glucose in each group were monitored. By the end of the experiment, mice were sacrificed, and POMC protein expression and STAT3 mRNA expression in hypothalamus were detected.Results:There were no significant differences in body weight and blood glucose levels among all groups at baseline( P>0.05). The differences of body weight and blood glucose levels among various groups were compared at 3, 6, 9 and 12 weeks after the model was established. The results showed that body weight of mice in the diabetes group or miR-21 knockout+ diabetes group was higher than that in the control group at each time point( P<0.05). Moreover, there were significant difference in body weight between diabetes group and miR-21 knockout+ diabetes group at 3 and 12 weeks( P<0.05). The blood glucose levels in diabetes group were significantly higher than those in other groups at each time point( P<0.05). The blood glucose level in miR-21 knockout+ diabetes group was lower than that in diabetes group and higher than control group( P<0.05). POMC protein and STAT3 mRNA levels in diabetes group were significantly lower than those in control group, while those in the miR-21 knockout+ diabetes group were higher than those in the diabetes group. Conclusions:The expression of POMC in hypothalamus of miR-21 knockout mice is higher than that of wild-type diabetic mice. miR-21 knockout can decrease blood glucose level and body weight, and improve energy metabolism of diabetic mice.
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Objective To analyze the correlation between urinary albumin/creatinine ratio (ACR) and 24-hour urinary microalbumin (UMA) and evaluate the predictive value of ARC for early diabetic nephropathy.Methods A total of 368 patients with type 2 diabetes mellitus were retrospectively collected.Early diabetic nephropathy was defined as 24h UMA 30～＜300 mg/24h.The correlation between ACR and 24hUMA,and the area under the receiver operating characteristic (ROC) curve of ACR in diagnosis of early diabetic nephropathy were calculated.Gender,age,course of disease,fasting venous blood glucose,glycosylated hemoglobin,blood pressure,triglyceride and total cholesterol were used as adjusting variables to establish univariate and multivariate logistic models of ACR for early diabetic nephropathy,respectively.A regression model was used to evaluate the diagnostic value of ACR for early diabetic nephropathy.Results The correlation between ACR and 24h UMA was 0.658.The area under ROC curve of ACR for early diabetic nephropathy was 0.907 before and 0.933 after adjustments of gender,age,course of disease,fasting venous blood glucose,glycosylated hemoglobin,blood pressure,triglyceride and total cholesterol,respectively.The OR value of ACR of diabetic nephropathy was 2.016 before and 2.762 after same adjustments.The calibration of Hosmer-Lemeshow chi-square test evaluation model was 19.362 before (P=0.13) and 14.928 after adjustments (P=0.061).Conclusion ACR is a better predictor for early diabetic nephropathy although its value is influenced by gender,age,course of disease,blood sugar,lipid,and blood pressure.
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Objective To observe the changes of serum and fecal taurine-conjugated bile acid levels and its association with glucose metabolism during the spontaneous development of type 2 diabetes in OLETO rats.Methods Twenty male OLETF rats(4 weeks old)were included and 10 male LETO rats of the same age were used as the normal control group.OLETF rats were fed with high fat diet whereas LETO rats were fed with normal diet.Serum and fecal taurine-conjugated bile acid levels of OLETF rats were tested at different stage of diabetes including baseline, normal glucose tolerance, impaired glucose tolerance and diabetes periods, and the association of taurine-conjugated bile acid level with body weight, blood glucose, and glucose-regulating hormones were also investigated.Results Compared with LETO rats, the baseline serum levels of taurine-conjugated bile acid in OLETF rats did not change, but the levels of fecal taurine-conjugated bile acid including taurine-conjugated chenodeoxycholic acid(TCDCA), taurocholic acid(TCA)and taurine-conjugated deoxycholic acid(TDCA)were significantly decreased [(14.25±7.18 vs 0.90±0.31)mg/kg,(7.12±4.14 vs 1.30±0.35)mg/kg,(4.30±1.78 vs 1.02±0.14)mg/kg, all P<0.01].During the development of diabetes, the fecal levels of TCDCA, TCA and TDCA were still lower than those in the control rats.TDCA was negatively associated with the level of fasting blood glucose(r=-0.470, P=0.032),but positively associated with the serum level of glucagon-like peptide(GLP)-l(r=0.406, P=0.044).Conclusion The decrease of intestinal taurine-conjugated bile acid level is involved in the development of diabetes in OLETF rats.Intestinal TDCA may regulate the secretion of GLP-1 by paracrine pathway.