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 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.