ABSTRACT
Objective To explore the effects of high fat diet on insulin resistance ( IR) and the expression of liver insulin receptor substrate ( IRS) 1 and 2 in Tibet minipigs. Methods Ten Tibet minipigs were randomly divided into 2 groups, normal control (Ctr, n=5) group was fed with normal diet, and IR model (n=5) group fed with high fat/choles-terol diet for 12 weeks. After the establishment of pig models for 12 weeks, the body weight and body length were measured and body mass index ( BMI) was calculated, and the changes of total cholesterol ( TC) , low density lipoprotein ( LDL?C) , high density lipoprotein ( HDL?C) , triglyceride ( TG) , free fatty acids ( FFA) , fasting blood glucose ( FBG) , fasting insu?lin ( insulin) and homeostasis model assessment?insulin resistance ( HOMA?IR) were detected. Glucose tolerance test was performed, the area under the curve of glucose tolerance ( AUC) was also calculated, and the expressions of IRS?1 and IRS?2 gene and protein in liver tissue were detected. The lipid deposition, liver glycogen and pathological changes were ex?amined by pathology using oil?red O, PAS and HE staining, respectively. Results Compared with the control group, the body weight, BMI index, TC, LDL?C, HDL?C, FFA, FBG, insulin and HOMA?IR were significantly increased ( P <0. 05, P<0. 01). Intravenous glucose tolerance test showed that the curve of blood glucose and insulin levels were slowed down, while AUCglucose and AUCinsulin were significantly increased (P<0. 05, P<0. 01). Lipid deposition and liver glyco?gen were increased, and partial hepatocyte swelling, part of the nuclei disappeared or were pushed to one end, occasionally scattered infiltration of lymphocytes in the liver tissue. Furthermore, the expressions of IRS?1 and IRS?2 mRNA and protein were significantly decreased (P<0. 05, P<0. 01). Conclusions High fat diet can induce insulin resistance in Tibet minipigs. The decreased IRS?1 and IRS?2 expression in the liver may be one of the molecular mechanisms involved in the effects of high fat diet on insulin sensitivity in Tibet minipigs.
ABSTRACT
Objective The study was carried out to investigate the effects of different dietary Ca levels on bone metabolism, based on the osteoprotegerin ( OPG)-receptor activator of NF?κB ligand ( RANKL)?receptor activator of NF?κB ( RANK) system in growing WHBE rabbits. Methods Twenty one weaned male WHBE rabbits at the age of 42 days were divided into 3 groups (I, II and III) according to dietary Ca levels (0. 95%, 1. 10%, and 1. 30%, respectively) for a 42?d feeding trial. The above three diets had similar phosphor (P) (about 0. 64 g/kg), digestible energy (9. 50 MJ/kg), crude protein (about 19. 70%) and crude fibre (13. 57%) contents. When the feeding trial finished, the serum in?dices of bone metabolism (Ca, PTH and BALP) were detected, and the OPG?RANK?RANKL system in bone tissue was analyzed by real?time fluorescence quantitative PCR assay and immunohistochemistry, respectively. At last, the relationships between bone metabolism and dietary Ca were evaluated according to RANKL/OPG ratio. Results All the contents of serum Ca, PTH and BALP had no significant differences in the groups I, II and III (P>0. 05). Both the RANKL mR?NA and RANKL/OPG mRNA ratio were lowest in the group II and had significant differences with group I and III ( P<0. 05). Dietary Ca levels had significant effects on the protein expression of OPG?RANK?RANKL in bone tissues (P<0. 01). The positive index of OPG in the groups II and III was significantly higher than that in the group I(P<0. 01), while the positive index of RANK in the group II was lower than those of the group I and III(P<0. 01). The protein ex?pression positive index ratio of RANKL to OPG was also lowest in the group II, showing a significant difference with group I(P<0. 01). Furthermore, both the gene transcription ratio of RANKL to OPG and the protein expression positive index ratio of RANKL to OPG had significant correlations (with quadratic curve) to the dietary Ca levels (R2 =0. 4068, 0. 8433;P<0. 05,P<0. 001). Conclusions In summary, the bone metabolism of WHBE rabbits during growing periods has sig?nificant correlation with dietary Ca levels. An optimal bone metabolism status can be obtain at 1. 10% dietary Ca level as demonstrated in this study.
ABSTRACT
Objective To observe the intervention effect of salvianolic acid A ( SAA) on retinopathy of Zucker diabetic fatty ( ZDF ) rats and explore the possible action mechanism of SAA to prevent and treat diabetic retinopathy ( DR) . Methods Thirty-two 7-8-week old ZDF rats were taken and fed with Purina rat chow for 4 weeks. The ZDF rats were equally divided by the blood glucose into model group, 0. 5 mg/kg SAA group, 1. 0 mg/kg SAA group and metformin ( Met) group. 8 Zucker lean ( ZL) rats were taken as control group. After 12-week administration, incidence of cataracts and retinal pathology was observed, and levels of GLU, TC and HbA1c in blood, transferrin ( TRF) and retinol binding protein ( RBP) in urine and levels of interleukin-1 ( IL-1 ) , interleukin-6 ( IL-6 ) , oxidized low density lipoprotein ( ox-LDL), malondialdehyde (MDA) and lipoprotein related phospholipase A2 (Lp-PLA2) activity in serum were measured. Results In the model group, GLU, TC, HbA1c , diabetic cataract incidence rate, retinal basement thickening and microangiopathy appeared in most of the rats. The levels of TRF and RBP in urine and levels of IL-1, IL-6, ox-LDL, MDA in serum were significantly increased, and Lp-PLA2 activity was also significantly increased. After SAA administration, the morbidity rate of cataract was reduced, and retinal pathological changes were improved in different degrees. The levels of TRF, RBP, IL-1, IL-6, ox-LDL, MDA and Lp-PLA2 activity was decreased. Conclusions SAA can slow down the process of diabetic retinopathy in ZDF rats and reduce the incidence of cataract. The mechanisms of action may be related to inhibition of chronic inflammation, prevention of lipid peroxidation and reduction of Lp-PLA2 activity.
ABSTRACT
Objective To observe the intervention effect of salvianolic acid A ( SAA) on retinopathy of Zucker diabetic fatty ( ZDF ) rats and explore the possible action mechanism of SAA to prevent and treat diabetic retinopathy ( DR) . Methods Thirty-two 7-8-week old ZDF rats were taken and fed with Purina rat chow for 4 weeks. The ZDF rats were equally divided by the blood glucose into model group, 0. 5 mg/kg SAA group, 1. 0 mg/kg SAA group and metformin ( Met) group. 8 Zucker lean ( ZL) rats were taken as control group. After 12-week administration, incidence of cataracts and retinal pathology was observed, and levels of GLU, TC and HbA1c in blood, transferrin ( TRF) and retinol binding protein ( RBP) in urine and levels of interleukin-1 ( IL-1 ) , interleukin-6 ( IL-6 ) , oxidized low density lipoprotein ( ox-LDL), malondialdehyde (MDA) and lipoprotein related phospholipase A2 (Lp-PLA2) activity in serum were measured. Results In the model group, GLU, TC, HbA1c , diabetic cataract incidence rate, retinal basement thickening and microangiopathy appeared in most of the rats. The levels of TRF and RBP in urine and levels of IL-1, IL-6, ox-LDL, MDA in serum were significantly increased, and Lp-PLA2 activity was also significantly increased. After SAA administration, the morbidity rate of cataract was reduced, and retinal pathological changes were improved in different degrees. The levels of TRF, RBP, IL-1, IL-6, ox-LDL, MDA and Lp-PLA2 activity was decreased. Conclusions SAA can slow down the process of diabetic retinopathy in ZDF rats and reduce the incidence of cataract. The mechanisms of action may be related to inhibition of chronic inflammation, prevention of lipid peroxidation and reduction of Lp-PLA2 activity.