1.Effects of diacerein on inflammatory cytokines and adipose metabolism as well asthe expression of chemerin in adipose tissue of type 2 diabetic rats
Zhilei HUANG ; Xiaojun HUANG ; Xiaoli HUANG ; Fuzhen LIU ; Niaona HU ; Guixin HUANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2017;38(5):693-697,729
Objective To study the effects of diacerein and its metabolite rhein on plasma inflammatory cytokine level and expression of perirenal adipose tissue chemerin in type 2 diabetes mellitus (T2DM) rats and its role in regulating glucose and lipid metabolism.Methods We randomly divided 56 SD male rats into 5 groups: normal control group (Group A), T2DM group (Group B), pioglitazone group (Group C), diacerein group (Group D), and pioglitazone+diacerein group (Group E).Group A was fed with ordinary feed whereas the other groups were fed with high-fat diet.At the end of week 8, rats in Groups B, C, D and E were injected intraperitoneally with 30mg/kg of STZ solution to create the model.Those in Group A were injected with the same volume of sterile sodium citrate solution.OGTT examination was taken to screen the model rats at the end of week 10.The successful mode was chosen according to OGTT result.Then Group C was treated with pioglitazone 10mg/(kg·d) orally, Group D with diacerein 50mg/(kg·d), Group E with pioglitazone 10mg/(kg·d)+diacerein 50mg/(kg·d), and Group A and B were given the same volume of normal saline.The intervention lasted 4 weeks.At the end of experiment weeks 10 and 14, FBG, FINS, TC, TG, LDL-C, IL-1β, IL-6, and TNF-α were detected in the fasting rats with free access to water.After blood sample was taken at the end of week 14, all rats were killed and theperirenal adipose tissue was isolated, the expression of chemerin in perirenal adipose tissue was detected by Western blotting.Results At the end of week 10, FBG, FINS, TG, TC, LDL-C, IL-1β, IL-6, and TNF-α were higher in Groups B, C, D and E than in Group A while HDL-C was lower (all P<0.01).At the end of week 14, TC, TG, and LDL-C were lower in Groups C, D and E than in Group B but higher than Group A while HDL-C was lower than in Group A (all P<0.05).Group E had greater changes in glucose and lipid metabolism and inflammatory cytokine level than Groups C and D (P<0.05).Western blotting results showed that the expression of chemerin in perirenal adipose tissue increased higher in Group B than in Groups A, C, D and E (P<0.05).The expression of chemerin were also higher in Groups C and D than in Groups A and E (P<0.05), but there was no significant difference between Groups A and E.Conclusion Diacerein can regulate the metabolism of glucose and lipid, improve insulin resistance by reducing the expression of chemerin and the level of inflammatory cytokines.
2.Effects of anti-inflammatory drugs of diacerein on glucose and lipid metabolism in type 2 diabetic rats
Xiaoli HUANG ; Xiaojun HUANG ; Fuzhen LIU ; Niaona HU ; Zhilei HUANG ; Guixin HUANG
Journal of Medical Postgraduates 2017;30(1):36-41
Objective Recent studies have shown that inflammatory cytokines are involved in the occurrence and development of diabetes mellitus .The article aimed to investigate the effects of anti-inflammatory drug--diacerein on hepatic PPAR-γand GLUT-2 protein expression and its role in the regulation of glucose and lipid metabolism in rats with type 2 diabetes mellitus ( T2DM) . Methods 55 male SD rats were randomly divided into 4 groups:normal control group (n=10), T2DM group (n=15), pioglitazone intervention group(n=15), and diacerein treatment group(n=15) .Rats in normal control group were fed with normal diet , the other 3 groups were fed with high fat diet .At the end of 8th experi-ment week, rats in 3 groups fed with high fat diet were treated with intraperitoneal injection of 30mg/kg streptozotocin ( STZ) solution, while rats in normal control group were injected with the same volume of sterile sodium citrate solution .At the end of 10th week, OGTT modeling rats were screened .Rats in pioglitazone intervention group were treated with 10 mg/kg pioglitazone by intragastric administra-tion, rats in diacerein group was treated with 50mg/kg diacerein by intragastric administration , and rats in normal control group and T2DM group were given the same volume of normal saline .The intervention lasted 4 weeks.At the end of 8th, 10th and 14th week, the blood examination of glycolipid , FINS, IL-1βand liver function indexes was done on fasting rats .Fourteenth weeks later , after getting blood samples , all rats were sacrificed and liver tissues were isolated .Western blot was applied in the detection of PPAR γand immu-nohistochemistry was applied to detect GLUT-2 protein in livers. Results At the end of 8th week, the FBG level in pioglitazone in-tervention group increased compared with normal control group ( P<0.05) , and the levels of TC , TG, FINS, LDL-C, ALT, AST, IL-1βin the other 3 groups increased significantly compared with normal control group (P<0.05).At the end of 10th week, in comparison with normal control group , the levels of FBG , FINS, TC, TG, LDL-C, ALT, AST and IL-1βincreased significantly ( P<0.05) , while the levels of HDL-C and ISI decreased significantly (P<0.01).Moreover, the levels of FINS, TC, TG, LDL-C, ALT, AST and IL-1βat 10th weekend increased significantly compared with those at 8th weekend(P<0.05).At the end of 14th week, the FBG levels in T2DM group, pioglitazone intervention group and diacerein treatment group were higher than that of normal control group (P<0.01), while compared with T2DM group, the FBG level in pioglitazone intervention group decreased and the levels of HbA 1c, TC, TG, LDL-C and ALT in pioglitazone intervention group and diacerein treatment group decreased ( P<0.05) along with the increased ISI and HDL-C levels ( P<0.05) .Compared with the results at 10th weekend , the levels of FBG , HbA1c, LDL-C, ALT, AST in T2DM group in-creased (P<0.05) while the levels of HbA1c, TC, ALT, AST and IL-1βin pioglitazone intervention group and diacerein treatment group decreased significantly at 14th weekend(P<0.01).The expression level of PPAR-γin pioglitazone intervention group (0.91± 0.03) was significantly higher than normal control group (0.82±0.15), T2DM group(0.75±0.28) and diacerein treatment group (0.83± 0.34) ( P<0.01) , and no significant difference was found between diacerein treatment group and normal control group( P>0 .05) show-ing higher levels compared with T 2DM group ( P<0.01).At 14th weekend, the GLUT-2 expression levels in normal control group (0.209±0.023), pioglitazone intervention group (0.226±0.017) and diacerein treatment group (0.232±0.012) were higher than that of T2DM group (0.173±0.009,P<0.01);and the GLUT-2 expression levels in pioglitazone intervention group and diacerein treatment group were higher than that of normal control group (P<0.05).The expression level of liver PPAR-γwas in positive correlation with those of GLUT-2 protein, HDL-C, FINS, ISI ( r=0.815, 0.780, 0.747, P<0.01) and in negative correlation with those of FBG , HbA1c, TC, TG, AST, ALT, IL-1β(r=-0.465,-5.716,-0.615,-0.675,-0.617,-0.521,-4.827, P<0.05). Conclusion Diacerein can enhance liver PPAR-γand GLUT-2 expression levels and reduce the levels of IL-1β, HbA1c and blood lipid, thus im-prove insulin resistance in T 2DM rats.