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The Goto-Kakizaki (GK) rat is a non-obese experimental model of type 2 diabetes mellitus (T2DM) that allows researchers to monitor diabetes-induced changes without jeopardizing the effects of obesity. This rat strain exhibits notable gastrointestinal features associated with T2DM, such as marked alterations in intestinal morphology, reduced intestinal motility, slow transit, and modified microbiota compared to Wistar rats. The primary treatments for diabetic patients include administration of hypoglycemic agents and insulin, and lifestyle changes. Emerging procedures, including alternative therapies, metabolic surgeries, and modulation of the intestinal microbiota composition, have been shown to improve the diabetic state of GK rats. This review describes the morpho-physiological diabetic-associated features of the gastrointestinal tract (GIT) of GK rats. We also describe promising strategies, e.g., metabolic surgery and modulation of gut microbiota composition, used to target the GIT of this animal model to improve the diabetic state.
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This study was aimed to investigate the mechanism of Danzhi Jiangtang Capsules( DJC) in the treatment of diabetic macrovascular disease in Goto-Kakizaki( GK) rats. The diabetic macrovascular disease rat model was induced by feeding high-fat and high-sugar combined with endothelial nitric oxide synthase( NOS) inhibitor N-nitro-L-arginine methyl ester( L-NAME)( 0. 1 g·L-1·d-1). According to the random array table,the model rats were randomly divided into the model group,DJC groups( 1 260,630,320 mg·kg-1),atorvastatin group( 105 mg·kg-1) and metformin group( 10 mg·kg-1),with 12 rats in each group. The rats received gavage administration for 8 weeks. Twelve Wistar rats were selected as the normal control group. The changes of body weight,water intake,blood glucose,plasma total cholesterol( TC),triglyceride( TG),high density lipoprotein( HDL-C),low density lipoprotein( LDL-C),interleukin( IL-1β),IL-6,tumor necrosis factor( TNF-α),nitric oxide( NO),endothelin( ET-1) were observed in these rats. Aortic tissue was taken and the pathological changes were observed by HE staining. RT-PCR was used to detect the mRNA levels of IL-1β,IL-6,and TNF-α in rat aorta. RT-PCR of the stem loop was used to detect the levels of miRNA-126,miRNA-155,miRNA-146 a,and miRNA-21 in rat plasma and aortic tissue. The canonical correlation between miRNAs and inflammatory factors was then analyzed. The results showed that DJC increased the rat body weight,lowered water intake,reduced the random blood glucose,reversed the rat aorta tissue damage,reduced serum TC,TG,LDL-C,ET-1,IL-1β,IL-6,TNF-α,as well as miRNA-155,miRNA-146 a and miRNA-21 levels in serum,elevated plasma HDL-C,NO content,reduced the aorta mRNA of IL-1β,IL-6,TNF-α,and the miRNA-155,miRNA-146 a and miRNA-21,elevated miRNA-126 expression in aorta. Aortic miRNA-126,miRNA-155,miRNA-146 a and miRNA-21 expression levels were typically correlated with the expression of inflammatory factors,among which miRNA-126 was negatively correlated,miRNA-155,miRNA-146 a and miRNA-21 were positively correlated with the factors. These results suggested that DJC had therapeutic effects on diabetic macrovascular diseases,and the mechanism of action may be related to the regulation of miRNA-126,miRNA-155,miRNA-146 a and miRNA-21 levels,as well as the reduction of inflammatory factors and vascular inflammatory response.
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Animals , Rats , Capsules , Diabetes Mellitus , Drugs, Chinese Herbal/therapeutic use , MicroRNAs , Rats, WistarABSTRACT
To investigate the protective effect of Yiqi Huoxue decoction on the kidney in diabetic goto-Kaizaki (GK) rats. Eight Wistar rats were used as normal control group. According to body weight and blood glucose, 16 GK rats were randomly divided into model control group and Yiqi Huoxue group, with 8 rats in each group. Drugs were administrated for 6 weeks. The rats were weighed and fasting blood glucose (FBG) were measured weekly; the glycosylated hemoglobin (HbALc) and 24 h metabolic rate were measured at the end of third and sixth weeks, at the same time, urine was collected to measure urinary glucose (U-GLU), urinary creatinine (U-CREA) and total proteinuria (U-TP) by biochemical method and calculate 24 h protein excretion rate (UAER). At the end of treatment, rats were sacrificed in anesthesia, and creatinin (CREA), uric acid (UA) and cholesterol (CHOL) were detected by biochemical method and glutathione peroxidase (GSH-Px) was detected by manual method with the blood drawn from heart. Both kidneys were taken and weighed to calculate the renal hypertrophy index. The kidneys were placed into neutral formalin and observed under light microscope for pathological change after Periodic Acid-Schiff (PAS) staining. The results showed that as compared with the normal control group, FBG, HbALc, 24 h Metabolic rate, U-GLU, UAER, serum CREA, UA and CHOL levels, as well as renal hypertrophy index were significantly increased (<0.05) in the model group, while the body weight growth rate, serum GSH-Px level were significantly reduced(<0.05); in addition, renal glomerular injury and structural changes were observed in the model group. As compared with the model group, serum GSH-Px level was significantly increased (<0.05) in the Yiqi Huoxue group, While FBG, HbALc, 24 h Metabolic rate, U-GLU, UAER, serum CREA, UA and CHOL levels, as well as renal hypertrophy index were significantly reduced (<0.05); meanwhile, renal glomerular injury and structural changes were improved in the Yiqi Huoxue group. The results showed that Yiqi Huoxue decoction can significantly increase serum GSH-Px level, reduce FBG, HbALc, 24 h metabolic rate, U-GLU, UAER, serum CREA, UA and CHOL levels, as well as renal hypertrophy index, and improve renal pathology in diabetic GK rats.
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Objective To study the pathological features of two huge spontaneous tumors in Wistar and GK rats. Methods Forty Wistar rats and 40 GK rats were included in this study. Among those rats, two huge spontaneous tumors were observed in a Wistar rat at 14 months of age and in a GK rat at 22 months of age. The growth and survival status of the tumor?bearing rats were recorded. The tumors were surgically removed, and their pathological features were examined using HE and immunohistochemical staining (vimentin, CK19, α?SMA, CD31, CD34, S?100, NF及Ki?67). Results Both the two tumors were completely resected by surgery without much difficulties, and both host rats survived well after the operation. The weight of the two huge tumors was 502 g and 119 g, which corresponding to 64% and 24% of the body weight of their host rats, respectively. The tumors surface had a complete capsule, with a clear boundary separating from the normal surrounding tissues, and no vascular pedicle structure was found. According to the results of immunohistochemical staining, both the two tumors were diagnosed as benign fibroma. Conclusion This type of huge spontaneous tumors is benign fibroma. Besides the impact on the activities of the rats, the tumors have no significant impact on the living conditions in the hosts.
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Objective:To explore application of targeted contrast enhanced ultrasonography in diagnosis of early stage vascular endothelial injury and diabetic nephropathy.Methods:Targeted SonoVue-TM microbubble was prepared by attaching anti-TM monoclonal antibody to the surface of ordinary micro-bubble SonoVue by biotin-avidin bridge method and ultrasonic instrument was used to evaluate the developing situation of targeted microbubble in vitro. Twenty 12-week-old male GK rats and 20 Wistar rats were enrolled in this study, and were randomly divided into targeted angiography group and ordinary angiography group. Targeted microbubbles SonoVue-TM or general microbubble SonoVue were rapidly injected to the rats via tail vein; the developing situation of the two contrast agents in rats kidneys was dynamically observed. Time intensity curve was used to analyse rat kidney perfusion characteristics in different groups. Results:Targeted ultrasound microbubble SonoVue-TM was successfully constructed, and it could be used to develop an external image. Targeted microbubbles SonoVue-TM enabled clear development of experimental rat kidney. Time intensity curve shapes of rat kidney of the two groups showed as single apex with steep ascending and slowly descending branch. Compared with the control group, the rising slope of the GK rat renal cortex, medulla in targeted angiography group increased(P<0.05); the peak intensity of medulla increased (P<0.05), and the total area under the curve of medulla increased (P<0.05). Compared with control group, the ascending branch of the GK rat in renal cortex, medulla in ordinary angiography group increased (P<0.05). The peak intensity of the curve increased (P<0.05), and the total area under the curve increased (P<0.05). Compared with the ordinary angiography group, the peak of GK rat medullacurve in targeted angiography group intensity increased (P<0.05), and the total area under the curve increased (P<0.05).Conclusions:Targeted microbubbles SonoVue-TM can make a clear development of experimental rat kidney, its stable performance meet the requirement of ultrasonic observation time limit, and it can reflect early changes of blood perfusion in GK rat kindey.
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Objective: To explore application of targeted contrast enhanced ultrasonography in diagnosis of early stage vascular endothelial injury and diabetic nephropathy. Methods: Targeted SonoVue-TM microbubble was prepared by attaching anti-TM monoclonal antibody to the surface of ordinary microbubble SonoVue by biotin - avidin bridge method and ultrasonic instrument was used to evaluate the developing situation of targeted microbubble in vitro. Twenty 12-week-old male GK rats and 20 Wistar rats were enrolled in this study, and were randomly divided into targeted angiography group and ordinary angiography group. Targeted microbubbles SonoVue-TM or general microbubble SonoVue were rapidly injected to the rats via tail vein; the developing situation of the two contrast agents in rats kidneys was dynamically observed. Time-intensity curve was used to analyze rat kidney perfusion characteristics in different groups. Results: Targeted ultrasound microbubble SonoVue-TM was successfully constructed, and it could be used to develop an external image. Targeted microbubbles SonoVue-TM enabled clear development of experimental rat kidney. Time-intensity curve shapes of rat kidney of the two groups showed as single apex with steep ascending and slowly descending branch. Compared with the control group, the rising slope of the GK rat renal cortex, medulla in targeted angiography group increased (P < 0.05); the peak intensity of medulla increased (P < 0.05), and the total area under the curve of medulla increased (P < 0.05). Compared with control group, the ascending branch of the GK rat in renal cortex, medulla in ordinary angiography group increased (P < 0.05). The peak intensity of the curve increased (P < 0.05), and the total area under the curve increased (P < 0.05). Compared with the ordinary angiography group, the peak of GK rat medulla curve in targeted angiography group intensity increased (P < 0.05), and the total area under the curve increased (P < 0.05). Conclusions: Targeted microbubbles SonoVue-TM can make a clear development of experimental rat kidney, its stable performance meet the requirement of ultrasonic observation time limit, and it can reflect early changes of blood perfusion in GK rat kindey.
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The Goto-Kakizaki (GK) rat is a spontaneous type 2 diabetic animal model, which is characterized by a progressive loss of beta islet cells with fibrosis. In the present study, the hypoglycemic effect of asiatic acid (AA) in GK rats was examined. GK rats receiving AA at a daily dose of 25 mg·kg(-1) for four weeks showed a significant reduction in blood glucose levels. Age-matched normal Wistar rats were given 0.5% sodium carboxymethyl cellulose (CMC-Na) solution for the same periods and used as control. Compared to the normal Wistar rats, GK rats treated with AA showed improvement in insulin resistance partially through decreasing glucose level (P < 0.01) and insulin level (P < 0.05). Furthermore, the results of immunohistochemistry indicate that AA treatment reduced islet fibrosis in GK rats. Fibronectin, a key protein related to islet fibrosis, was over-expressed in GK rats, which was reversed significantly by AA treatment (P < 0.05). These findings suggest that AA has a beneficial effect on lowering blood glucose levels in GK rats and improves fibrosis of islets in diabetes, which may play a role in the prevention of islets dysfunction.
Subject(s)
Animals , Male , Blood Glucose , Metabolism , Centella , Chemistry , Diabetes Mellitus, Type 2 , Drug Therapy , Pathology , Disease Models, Animal , Fibronectins , Metabolism , Fibrosis , Glucose Tolerance Test , Hyperglycemia , Drug Therapy , Pathology , Insulin , Blood , Insulin Resistance , Islets of Langerhans , Pathology , Pancreatic Diseases , Metabolism , Pathology , Pentacyclic Triterpenes , Pharmacology , Therapeutic Uses , Phytotherapy , Plant Extracts , Pharmacology , Therapeutic Uses , Rats, Inbred StrainsABSTRACT
OBJECTIVE: To study on glucolipid metabolism effect of the total flavones of propolis (TFP) in Goto-Kakisaki rats (GK Rats). METHODS: Fifty GK rats were randomly divided into 5 groups by blood glucose, the model group, positive drug group (2 000 mg · kg-1) and the high (240 mg · kg-1) dose of the TFP group, the medium (120 mg · kg-1) doses of the TFP group, low (60 mg · kg-1) doses of the TFP group. The GK rats in TFP groups were given with TFP by intragastric administration, continuously treated for 8 weeks, the control group were given equal sodium carboxymethylcellulose(CMC-Na) and positive drug group were given (2 000 mg · kg-1) dose of Xiaoke pills by intragastric administration. The glucose (Glu), total cholesterol (TC), triglyceride (TG), high density lipoprotein(HDL-C), low density lipoprotein(LDL-C), glycated hemoglobin(GHb), superoxide dismutase (SOD), ma-londialdehyde(MDA), glutathione(GSH), serum insulin(lNS), C-peptide(C-P), tumor necrosis factor-α(TNF-α) free fatty acid (FFA), nitric oxide(NO), and hepatic glycogen were measured at the end of the experiment. RESULTS: Compared with the control group, the levels of GLU, TG, TC, LDL-C, GHb, MDA and TNF-α were decreased significantly (P 0.05) in the low-dose group. The levels of SOD, hepatic glycogen, NO and C-P were increased significantly(P < 0.05 or P < 0.01), the levels of GLU, MDA, TG and GHb were decreased significantly (P < 0.05 or P < 0.01 or P < 0.001) in Xiaoke pills group. CONCLUSION: TFP can significantly decrease the level of blood glucose, significantly improve the glucose and lipid metabolism and inhibit insulin resistance in deficiency of GK rats.
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OBJECTIVE@#To explore application of targeted contrast enhanced ultrasonography in diagnosis of early stage vascular endothelial injury and diabetic nephropathy.@*METHODS@#Targeted SonoVue-TM microbubble was prepared by attaching anti-TM monoclonal antibody to the surface of ordinary microbubble SonoVue by biotin - avidin bridge method and ultrasonic instrument was used to evaluate the developing situation of targeted microbubble in vitro. Twenty 12-week-old male GK rats and 20 Wistar rats were enrolled in this study, and were randomly divided into targeted angiography group and ordinary angiography group. Targeted microbubbles SonoVue-TM or general microbubble SonoVue were rapidly injected to the rats via tail vein; the developing situation of the two contrast agents in rats kidneys was dynamically observed. Time-intensity curve was used to analyze rat kidney perfusion characteristics in different groups.@*RESULTS@#Targeted ultrasound microbubble SonoVue-TM was successfully constructed, and it could be used to develop an external image. Targeted microbubbles SonoVue-TM enabled clear development of experimental rat kidney. Time-intensity curve shapes of rat kidney of the two groups showed as single apex with steep ascending and slowly descending branch. Compared with the control group, the rising slope of the GK rat renal cortex, medulla in targeted angiography group increased (P < 0.05); the peak intensity of medulla increased (P < 0.05), and the total area under the curve of medulla increased (P < 0.05). Compared with control group, the ascending branch of the GK rat in renal cortex, medulla in ordinary angiography group increased (P < 0.05). The peak intensity of the curve increased (P < 0.05), and the total area under the curve increased (P < 0.05). Compared with the ordinary angiography group, the peak of GK rat medulla curve in targeted angiography group intensity increased (P < 0.05), and the total area under the curve increased (P < 0.05).@*CONCLUSIONS@#Targeted microbubbles SonoVue-TM can make a clear development of experimental rat kidney, its stable performance meet the requirement of ultrasonic observation time limit, and it can reflect early changes of blood perfusion in GK rat kindey.
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Exercise training (ET) and selenium (SEL) were evaluated either individually or in combination (COMBI) for their effects on expression of glucose (AMPK, PGC-1alpha, GLUT-4) and lactate metabolic proteins (LDH, MCT-1, MCT-4, COX-IV) in heart and skeletal muscles in a rodent model (Goto-Kakisaki, GK) of diabetes. Forty GK rats either remained sedentary (SED), performed ET, received SEL, (5 micromol/kg body wt(-1)/day(-1)) or underwent both ET and SEL treatment for 6 wk. ET alone, SEL alone, or COMBI resulted in a significant lowering of lactate, glucose, and insulin levels as well as a reduction in HOMA-IR and AUC for glucose relative to SED. Additionally, ET alone, SEL alone, or COMBI increased glycogen content and citrate synthase (CS) activities in liver and muscles. However, their effects on glycogen content and CS activity were tissue-specific. In particular, ET alone, SEL alone, or COMBI induced upregulation of glucose (AMPK, PGC-1alpha, GLUT-4) and lactate (LDH, MCT-1, MCT-4, COX-IV) metabolic proteins relative to SED. However, their effects on glucose and lactate metabolic proteins also appeared to be tissue-specific. It seemed that glucose and lactate metabolic protein expression was not further enhanced with COMBI compared to that of ET alone or SEL alone. These data suggest that ET alone or SEL alone or COMBI represent a practical strategy for ameliorating aberrant expression of glucose and lactate metabolic proteins in diabetic GK rats.
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Animals , Rats , Area Under Curve , Citrate (si)-Synthase , Glucose , Glycogen , Heart , Insulin , Lactic Acid , Liver , Muscle, Skeletal , Muscles , Proteins , Rodentia , Selenium , Up-RegulationABSTRACT
Objective To investigated the effect of TangNaiKang (TNK) on VEGF protein expression of GK rats Thoracic aorta. Methods 51 male GK rats were divided into five groups randomly: model group, pioglitazone group, and TNK treatment group (low, immediate and high dose). Another 10 male Wistar rats were served as normal control group. GK rats were fed with high-grease forage, while normal control group was fed with a standard diet. Fasting blood glucose, general HE staining and VEGF protein expression were detected by immunohistochemistry. Results The fasting glucose had a significant decline in TNK treatment groups. HE staining showing TNK can ameliorate intima thickness, reduce hyperplasia of shallow vascular smooth muscle cell, and improve wavy and plexiform arrangement of elastic lamina. Immunohistochemistry also showed that TNK decreased VEGF protein expression of great vessels. Conclusion TangNaiKang can prevent and cure diabetic vascular complication of GK rats.
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Aim To observe the thickness changes of cardiomyocyte and microvascular basement membranes(BM)and the expression of collagen Ⅳ in Gk rats of different months and STZ-induced diabetic rats,and to explore the method that operated easily and could assess the thickness of myocardial BM.Methods GK rats of the fourth,fifth,sixth,seventh months,Streptozotocin induced diabetes rats of fifth months and normal Wister rats were respectively divided into different groups with ev eight rats in each group.The myocardial section was stained by methenamine silver and immunohistochemistry was performed for collagen Ⅳ.Left ventricular endocardium was selected as measuring view.Through computer image analysis,the ratio of BM positive staining density(BMPSD)and positive staining density of collagen Ⅳ(CPSD)were calculated separately in all myocardium.Take the ratio to assess the thickness of myocardial BM and the expression of collagen Ⅳ.Results The glycemia,BMPSD and CPSD of the two diabetes rats were higher than those of the normal rats,having highly remarkable difference(P0.05).Conclusion By methenamine silver staining for myocardial section,calculating BMPSD through computer image analysis,can be an index to assess the thickness of myocardial BM.
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AIM: To explore the anti-low-grade-inflammation mechanisms of Shenqi Compound Recipe(SQCR) in GK rats. METHODS: Specefic pathogen free(SPF) GK rats were divided randomly according to blood glucose level into four groups:Model,Ramipril,SQCR low dosage,SQCR high dosage group and normal Wistar rats(normal control group).GK rats were injected N-?-nitrol-L-arginine methyl ester(L-NAME) intra-peritoneally and took high-fat diet and Wistar rats were injected saline intra-peritoneally and took common diet freely,respectively.In the experiment periods,each group was administrated correspondent substance respectively for 32 days.Serum concentrations of C reactive protein(CRP) and adiponectin were determined by ELISA.Adiponectin mRNA expressions in white adiposed tissue were measured by real time reverse transcriptase PCR. RESULTS:Concentrations of CRP all decreased(P