RESUMO
Objective: The aim of this study was to investigate the anti-hyperglycemia effect and mechanism of aqueous extract from Gynostemma pentaphyllum (GP) leaves on STZ-induced diabetic rats. Methods: Diabetic rat models were established by intraperitoneal injection of streptozotocin (STZ, 50 mg/kg). A total of 21 successful SD male rats were randomly divided into model group (STZ). G. pentaphyllum leaves aqueous extract low dose group (GP•H2O-L, 100 mg/kg) and high dose group (GP•H2O-H, 500 mg/kg), another seven normal rats were taken as the control group. Blood samples were taken from the 2nd and 3rd weekends to detect plasma glucose and triglyceride concentrations; Real-time PCR was used to detect the expression of TNF-α and GLUT-4 mRNA in skeletal muscle; Western blotting was used to detect GLUT-4 total protein in skeletal muscle; The expression of GLUT-4 protein on skeletal muscle sarcolemma was observed by immunofluorescence staining. Results: The results showed that the food intake and water intake of the STZ group were significantly increased compared with the control group, while the body weight and skeletal muscle weight were obviously decreased; Plasma triglyceride and blood glucose concentrations and the expression of TNF-α mRNA in skeletal muscle were significantly increased, while the expression of GLUT-4 mRNA, GLUT-4 total protein and GLUT-4 protein in skeletal muscle sarcolemma was obviously decreased. Compared with the STZ group, the high-dose aqueous extract of G. pentaphyllum leaves significantly reduced the blood glucose of STZ-induced diabetic rats, and reversed the expression of TNF-α mRNA and GLUT-4 protein in skeletal muscle. Conclusion: The aqueous extract from G. pentaphyllum leaves could reduce hyperglycemia in STZ-induced diabetic rats, and its mechanism may be related to increasing the expression of GLUT-4 protein on skeletal muscle sarcolemma and inhibiting skeletal muscle inflammation.
RESUMO
Objective To evaluate the changes in myocardial glucose transporter 4 ( GLUT4 ) membrane translocation in the rats with high-level spinal cord injury ( SCI ) . Methods Thirty-six clean-grade healthy adult male Sprague-Dawley rats, weighing 250-300 g, were divided into 3 groups using a random number table method: control group (group C, n=6), sham operation group (group S, n=6) and high-level SCI group (group SCI, n=24). The model of SCI was established by a modified Allen's method in anesthetized rats. The spinal cord was only exposed in group S. Six rats were selected in C and S groups and at 4, 12, 24 and 48 h after SCI ( T1-4 ) in group SCI, and blood samples were taken from the abdominal aorta to measure the activities of serum creatine kinase and creatine kinase isoenzyme-MB. The rats were then sacrificed, and myocardial specimens were collected for microscopic examination of the ultra-structure ( with a transmission electron microscope) and for determination of ATP weight ratio, phosphoryla-tion of insulin receptor substrate-1 tyrosine and expression of GLUT4 in cell membrane ( by Western blot) . Results Compared with C and S groups, the serum creatine kinase and creatine kinase isoenzyme-MB ac-tivities were significantly increased at T1-4 , the ATP weight ratio was decreased, the expression of GLUT4 in myocardial cell membrane was down-regulated, the expression of phosphorylated insulin receptor sub-strate-1 tyrosine in myocaradium was down-regulated at T2,3 (P＜0. 05), and the pathological changes of myocardial tissues were found in group SCI. There was no significant difference in the indexes mentioned a-bove between group C and group S ( P＞0. 05) . Conclusion The mechanism of myocardial energy metabo-lism disorder may be related to the reduced membrane translocation of GLUT4 in the rats with high-level SCI.
RESUMO
Objective To investigate the role of glucose transporter ( GLUT ) 2 and 4 in hyperuricemia-induced insulin resistance. Methods Male uric acid oxidase gene knock-out spontaneous hyperuricemia mice ( KO) and wild-type mice ( WT) were fed with high-fat diet to establish an insulin resistance model. Then, some of KO mice were treated with allopurinol for lowering uric acid. Uric acid, fasting plasma glucose (FPG), and fasting insulin ( FINS) were detected. Intraperitoneal glucose tolerance test ( IPGTT ) and insulin tolerance test ( ITT ) were performed. Finally, the expression levels of Slc2a4 and Slc2a2 mRNA in tissues were determined by real-time PCR, while those of GLUT2 and GLUT4 proteins in tissues were analyzed by Western blot. Results There was no significant difference in FPG among various groups. The level of FINS in KO group was significantly higher than that in WT group [(0.636± 0.07) vs (0.456 ± 0.03) ng/ml, P<0.01], with decreased insulin sensitivity and impaired glucose tolerance. The uric acid level in the KO group remained at a high level [ ( 549. 68 ± 48. 7 ) vs ( 216. 61 ± 27. 5 )μmol/L] . After uric acid level in KO mice was reduced by allopurinol, insulin sensitivity and glucose metabolism were improved. Compared with WT group, the expression levels of Slc2a4 and GLUT4 in the gastrocnemius muscle were decreased while the expression levels of Slc2a2 and GLTU2 in liver were increased in KO group, which were reversed by allopurinol-mediated uric acid reduction. Conclusion Uric acid may induce insulin resistance via decreasing Slc2a4/GLUT4 expressions in skeletal muscle, and increasing Slc2a2/GLTU2 expressions in liver.
RESUMO
This study was designed to investigate the therapeutic effect and mechanisms of action of novel compound N-(Z)-9-octadecenyl-2-propanesulfonamide (N15) on type 2 diabetes (T2DM). A mouse model of T2DM was established with multiple injection of streptozotocin (STZ) at a low dose. N15 at different doses (50, 100 and 200 mg·kg-1·d-1) and pioglitazone (6 mg·kg-1·d-1) were administrated orally for 6 weeks. The level of fasting blood glucose (FBG) and fasting insulin (FIns) were measured in the course of the experiment for insulin resistance index (HOMA-IR). Oral glucose tolerance test (OGTT) and intraperitoneal insulin tolerance test (IPITT) were determined in the treated mice. The expression of Akt, AMPK and Glut4 in liver were analyzed by Western blot. N15 was found to reduce the level of FBG, FIns and HOMA-IR (P P P P P > 0.05). These results suggested that the novel compound N15 can ameliorate insulin resistance and the potential mechanism may be associated with increased insulin signaling in liver and promotion of phosphatidyl inositol 3 phosphate phosphorylation.
RESUMO
To investigate the effects of Gegen Qinlian decoction(GQD) in improving adipocytic insulin resistance(IR) and explore its related molecular mechanism. Diabetic rats models were induced by high glucose and high-fat diet with a small dose of streptozotocin, and after GQD treatment for 3 months, blood biochemical indexes such as fasting blood-glucose(FBG), insulin, glycosylated serum protein(GSP) and HOMA-IRI were detected and assessed. After the total RNA was extracted from the adipose tissue of diabetic SD rats, PPARγ, ADPN, GLUT4, GLUT2, ACACA and ACACB mRNA expression levels were separately detected by qPCR. Then, stable IR-3T3-L1 adipocyte model was built with 1 μmol•L⁻¹ dexamethasone. After the cell viability was detected by CCK-8 assay, 5%, 10% and 15% GQD-containing serum(GQD-CS) were respectively used to treat IR-3T-L1 adipocytes for 24 h. The contents of glucose, nonesterified fatty acid(NEFA) and adiponectin in cell culture supernatants were separately detected whereas the intracellular triglyceride(TG) contents of IR-3T3-L1 adipocytes were also measured. The ADPN, PPARγ and GLUT4 mRNA and protein expression levels were respectively detected by qPCR and Western blot in IR-3T3-L1 adipocytes. Results showed that GQD significantly decreased fasting blood glucose, insulin and GSP(P<0.01), and down-regulated HOMA-IRI(P<0.05) after the high-fat diet/streptozotocin-induced diabetic SD rats were treated for three months, with a good hypoglycemic effect. Moreover, PPARγ, ADPN, GLUT4, GLUT2, ACACA and ACACB mRNA expression levels were significantly elevated in the adipose tissue of GQD-treated diabetic SD rats. The 5%, 10% and 15% GQD-CS significantly increased glucose consumption of IR-3T3-L1 adipocytes at 24 h treatment(P<0.01), significantly decreased the intracellular TG content (P<0.01), and down-regulated NEFA to a certain extent but not significantly. Moreover, GQD-CS significantly up-regulated GLUT4 and ADPN expression. The results indicated that GQD could activate PPARγ to ameliorate adipocytic insulin resistance in the diabetic SD rats and IR-3T3-L1 adipocytes.
RESUMO
Objective To evaluate the effect of Ji Tang Zhi on glucose metabolism in insulin resistance (IR) HepG 2 cell line,and to explore the related mechanism.Methods The HepG2 cells were incubated in culture medium addition of 10-7 mol/L insulin for 24 h to establish the IR cell model.Effect of Ji Tang Zhi on rate of glucose absorption in HepG2 cell was detected by the method of glucose oxidase-peroxidase (GOD-POD).We performed an MTT assay to determine cytotoxicity effects of Ji Tang Zhi on HepG2 cell line.The expression of p-IRS-1 Ser307,PI3K and GLUT-4 were detected by Western blotting.Results Incubated with 10-7 mol/L insulin for 24 h,the insulin resistance cell model had been built.Compared with model group,the rate of glucose absorption of cell treated with JTZ (30 ～ 120 μg/mL) was significantly improved.According to model cells,the expression of GLUT-4 and PI3K decreased significantly compared to control cells.While the expression of p-IRS-1 Ser 307 was inhibited and GLUT-4 and PI3K expression were increased in IR cells after treated with JTZ (30 ～ 120 μtg/mL).Conclusion JTZ exert beneficial effects on hyperglycosemia in IR cell line possibly through regulating the levels of GLUT-4,p-IRS-1 Ser307 and PI3K in HepG2 cell.
RESUMO
Objective To investigate the effect of desflurane post-processing on the expression of glucose transporter 4 (GIUT4)in myocardial ischemia-reperfusion injury.Methods Twenty-four male New Zealand white rabbits were randomly divided into 4 groups (n =6 each):normal control group (group NC),ischemic-reperfusion group (group IR),ischemic-reperfusion postconditioning group (group IRP),desflurane aftertreatment group (group Des).Myocardial ischemia-reperfusion model was established by ligating the left coronary artery.Plasma glucose,Insulin and myocardial glucose uptake rate were measured at the time point before ischemia (T0),30 min after ischemia (T1),30 min (T2),60 min (T3) and 120 min (T4) after reperfusion,for dynamic comparison;the expression of GLUT4 mRNA in myocardium was detected by quantitative RT-PCR,and GLUT4 protein was detected by Western blot.Results Compared with group NC,the levels of blood glucose at T2-T4 increased in group IR (P＜0.05),but blood glucose in group Des was significantly lower than that in groups IR and IRP at T2-T4 (P＜0.05).Compared with group NC,serum insulin levels in groups IR,IRP and Des were significantly higher at T1-T3 (P＜0.05).The level of serum insulin in groups IRP and Des at T1 and T2 was significantly higher than that in group IR (P＜0.05),while that in group Des was higher than that in group IRP (P＜0.05).Blood glucose uptake rate in group IR at T2-T4 was significantly lower than that in groups NC,IRP and Des (P＜0.05),while the blood glucose uptake rate was higher in group Des than that in group IRP (P＜0.05).compared with group NC,the expression of GLUT4 mRNA and protein in groups IR,IRP and Des decreased (P＜0.05),but compared with groups IR and IRP,GLUT4 mRNA and protein expression increased in group Des (P＜0.05).Conclusion Postconditioning of desflurane can improve myocardial ischemia-reperfusion insulin resistance and increase myocardial glucose uptake,which may be related to the increase of myocardial GLUT4 expression.
RESUMO
Objective To explore the effects of water extract from Jiangtang Decoction (WEJTD) on PI3K/Akt signal pathway of skeletal muscle metabolism in KK-Ay diabetic mice.Methods Totally 50 KK-Ay mice were randomly divided into five groups:model group,metformin (positive drug,250 mg/kg) group,WEJTD low,medium,and high dose (2,4,and 8 g/kg) group,with 10 C57BL/6J mice as normal group.The relative drugs were ig administered once a day for 12 weeks,and mice in control group and model group were perfused with distilled water of equal volume.After 12 weeks' oral administration,mice were executed to separate serum,serum insulin level was detected by ELISA kit method;RNA was extracted from muscle tissue by Trizol,and real-time PCR were used to detect the level of PI3K,Akt,GLUT-4,GSK-3β,GS and IRS-1 mRNA.Results WEJTD can down-regulate concentration of insulin in serum and GSK-3β mRNA in skeletal muscle (P ＜ 0.05 and 0.001),and down-regulate mRNA of PI3K,Akt,IRS-1,GLUT-4,and GS in skeletal muscle (P ＜ 0.05,0.01,and 0.001).Conclusion WEJTD decreased glycogen deposition and stimulated glucose transport in skeletal muscle through upregulation of PI3K/Akt signaling pathway.
RESUMO
Objective To investigate the effect of high uric acid(HUA) on insulin sensitivity (IS) in 3T3-L1 adipocytes and its mechanism. Methods 3T3-L1 adipocytes were pretreated with HUA with or without NAC,and then stimulated by insulin. The cell viability of 3T3-L1 adipocytes was detected by CCK-8 assay. The glucose consumption was measured by glucose oxidase method. The levels of phospho-IRS-1,phospho-Akt and GluT4 protein were tested by western blot. Results HUA could inhibit insulin-induced glucose consumption,phosphorylation of Akt (Thr308),dephosphorylation of IRS-1 (Ser307) and the GluT4 protein expression (P<0.05). All the above could be blocked by NAC(P<0.05). Conclusion HUA can inhibit inulin stimulated IRS-1/Akt signaling and GluT4 expression,and thus induced insulin resistance in 3T3-L1 adipocytes.
RESUMO
OBJECTIVE:To observe the effects of sitagliptin phosphate combine with acarbose on blood glucose,blood lipid and the serum glucose transporter 4(GLUT4)in elderly patients with type 2 diabetes. METHODS:86 elderly patients with type 2 diabetes were randomly divided into control group and observation group,43 cases in each group. All patients received guidance about diet,exercise and living habits,etc.,as well as the care about psychology and medication. Based on it,control group was given Acarbose tablet 50 mg/times,tid,chewing when a meal;observation group was given Acarbose tablet(the same dosage and usage)+ Sitagliptin phosphate tablet 100 mg/times,qd,orally. They were treated for 3 months. Fasting blood glucose(FBG),2 h postprandial blood glucose(2 hPG),glycosylated hemoglobin(HbAlc),body mass index(BMI),fasting insulin(FINs),insulin resistance index(HOMA-IR),islet B-cell function index(HOMA-B),total cholesterol(TC),triglyceride(TG),low-density lipo-protein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C)before and after treatment in 2 groups were compared, the incidence of adverse reactions was recorded. Other 43 healthy people were selected as healthy control group,the differences of serum GLUT4 levels before and after treatment between the 2 groups and healthy control group were respectively compared. RE-SULTS:After treatment,the BMI,FBG,2 hPG,HbAlc,HOMA-IR,FINs,TC,TG and LDL-C level were significantly lower than before,observation group was lower than control group;HOMA-B and HDL-C level were significantly higher than before,ob-servation group was higher than control group,with statistical significance(P0.05),while the serum GLUT4 level in observation group was significant higher than before and control group;and the serum GLUT4 level in 2 groups were still significant lower than healthy control group(P0.05). CON-CLUSIONS:Sitagliptin phosphate combine with acarbose can effectively control patients'blood glucose and lipid levels in the treatment of elderly patients with type 2 diabetes,improve HOMA-B and serum GLUT4 level,and does not increase the incidence of adverse reactions,with good safety.
RESUMO
Objective: To examine the effect of Pandanus amaryllifolius (P. amaryllifolius) leaf extract on the insulin resistance state in obese ICR mice. Methods: Obesity was induced in mice fed with high-fat diet (45%fat) for 12 weeks. After the first six weeks on the diet, the obese mice were administered with the water extract of P. amaryllifolius leaf at 125 and 250 mg/kg/day, respectively for another six weeks. At the 5th week of treatment, oral glucose tolerance test was conducted. After six weeks of treat-ment, the levels of blood glucose, serum insulin, leptin, adiponectin, and lipid profiles were determined. The liver, muscle and epididymal fat tissues were removed for measuring the biochemical parameters and protein expression, as well as histological examination. Results: Six weeks of treatment with P. amaryllifolius led to a significant reduction in the blood glucose level as well as improvement in the insulin resistance. P. amaryllifolius also increased the liver glycogen storage and serum adiponectin and decreased the serum leptin levels. A reduction in the serum and hepatic triglyceride, and non-esterified fatty acid levels was also observed. The histological examination showed that the obese mice treated with P. amaryllifolius reduced the lipid droplet in liver tissue and adipocyte size in epididymal fat tissue. The treatment also increased the protein expression of glucose transporter 4 in the muscle and fat tissues. Conclusions: The treatment with P. amaryllifolius could decrease several parameters of impaired glucose and lipid metabolism. To the best of our knowledge, this is the first report on the role of P. amaryllifolius leaf extract in alleviating the insulin dysfunction in obesity state.
RESUMO
Objective: To investigate the effect of Rhinacanthus nasutus (R. nasutus) leaf extract on impaired glucose and lipid metabolism in obese ICR mice. Methods: Obesity was induced in the male ICR mice by feeding them a high-fat diet (60 kcal% fat) for 12 weeks. After the first six weeks of the diet, the obese mice were administered with the water extract of R. nasutus leaves at 250 and 500 mg/kg per day for the next six weeks. Subsequently, the blood glucose, lipid profiles, insulin, leptin, and adiponectin levels were measured. The liver and adipose tissues were excised for his-topathological examination and protein expression study. Results: After six weeks of the treatment, R. nasutus extract (at 250 and 500 mg/kg per day) was found to reduce the elevated blood glucose level, improve the insulin sensitivity, decrease the serum leptin, and increase the serum adiponectin levels. The obese mice treated with R. nasutus were found to have a reduction in the increased lipid concen-trations in their serum and liver tissues. Moreover, treatment with R. nasutus reduced the fat accumulation in the liver and the large adipocyte size in the fat tissues. Interestingly, the administration with R. nasutus extract was marked by an increase in the hepatic peroxisome proliferators-activated receptor alpha, fat cell adiponectin, and glucose transporter 4 proteins. Conclusions: To the best of our knowledge, the present study is the first report on the impact of R. nasutus extract in improving the impaired glucose and lipid metabolism in high-fat diet-induced obesity in mice via stimulating the insulin sensitivity in the liver and adipose tissues.
RESUMO
Objective: To investigate the effect of Rhinacanthus nasutus (R. nasutus) leaf extract on impaired glucose and lipid metabolism in obese ICR mice. Methods: Obesity was induced in the male ICR mice by feeding them a high-fat diet (60 kcal% fat) for 12 weeks. After the first six weeks of the diet, the obese mice were administered with the water extract of R. nasutus leaves at 250 and 500 mg/kg per day for the next six weeks. Subsequently, the blood glucose, lipid profiles, insulin, leptin, and adiponectin levels were measured. The liver and adipose tissues were excised for histopathological examination and protein expression study. Results: After six weeks of the treatment, R. nasutus extract (at 250 and 500 mg/kg per day) was found to reduce the elevated blood glucose level, improve the insulin sensitivity, decrease the serum leptin, and increase the serum adiponectin levels. The obese mice treated with R. nasutus were found to have a reduction in the increased lipid concentrations in their serum and liver tissues. Moreover, treatment with R. nasutus reduced the fat accumulation in the liver and the large adipocyte size in the fat tissues. Interestingly, the administration with R. nasutus extract was marked by an increase in the hepatic peroxisome proliferators-activated receptor alpha, fat cell adiponectin, and glucose transporter 4 proteins. Conclusions: To the best of our knowledge, the present study is the first report on the impact of R. nasutus extract in improving the impaired glucose and lipid metabolism in high-fat diet-induced obesity in mice via stimulating the insulin sensitivity in the liver and adipose tissues.
RESUMO
Objective To examine the effect of Pandanus amaryllifolius (P. amaryllifolius) leaf extract on the insulin resistance state in obese ICR mice. Methods Obesity was induced in mice fed with high-fat diet (45% fat) for 12 weeks. After the first six weeks on the diet, the obese mice were administered with the water extract of P. amaryllifolius leaf at 125 and 250 mg/kg/day, respectively for another six weeks. At the 5th week of treatment, oral glucose tolerance test was conducted. After six weeks of treatment, the levels of blood glucose, serum insulin, leptin, adiponectin, and lipid profiles were determined. The liver, muscle and epididymal fat tissues were removed for measuring the biochemical parameters and protein expression, as well as histological examination. Results Six weeks of treatment with P. amaryllifolius led to a significant reduction in the blood glucose level as well as improvement in the insulin resistance. P. amaryllifolius also increased the liver glycogen storage and serum adiponectin and decreased the serum leptin levels. A reduction in the serum and hepatic triglyceride, and non-esterified fatty acid levels was also observed. The histological examination showed that the obese mice treated with P. amaryllifolius reduced the lipid droplet in liver tissue and adipocyte size in epididymal fat tissue. The treatment also increased the protein expression of glucose transporter 4 in the muscle and fat tissues. Conclusions The treatment with P. amaryllifolius could decrease several parameters of impaired glucose and lipid metabolism. To the best of our knowledge, this is the first report on the role of P. amaryllifolius leaf extract in alleviating the insulin dysfunction in obesity state.
RESUMO
Background: S. surattense is widely used in Siddha medicine for various ailments. Objective: The aim was to evaluate the impact of alcoholic leaf‑extract of S. surattense on mitochondrial enzymes in streptozotocin (STZ) induced diabetic rats and to study the in vitro muscle glucose uptake activity on L6 myotubes. Materials and Methods: The male albino Wistar rats were randomly divided into five groups of six animals each. Diabetes was induced by intraperitoneal injection of STZ (40 mg/kg body weight). After being confirmed the diabetic rats were treated with alcoholic leaf‑extract of S. surattense (100 mg/kg body weight) for 45 days. The biochemical estimations (liver mitochondrial enzymes, antioxidants, thiobarbituric acid reactive substances [TBARS]) and histopathological studies were performed. Further, the in vitro muscle glucose uptake activity in L6 myotubes and messenger RNA (mRNA) expression of glucose transporter‑4 (GLUT‑4) was performed. Results: In diabetic rats, the activities of liver mitochondrial enzymes were found to be significantly lowered. The mitochondrial TBARS level increased, whereas the activities/level of enzymatic and non‑enzymatic antioxidants decreased in diabetic rats. Administration of S. surattense to diabetic rats significantly reversed the above parameters toward normalcy. Furthermore in diabetic rats, the histopathological studies showed growth of adipose tissue and shrinkage of islets in the pancreas, liver showed fatty change with mild inflammation of portal triad, and kidney showed messangial capillary proliferation of glomeruli and fatty infiltration of tubules. Treatment with S. surattense brought back these changes to near normalcy. The extract was analyzed for in vitro muscle glucose uptake activity in L6 myotubes and mRNA expression of GLUT‑4 by semi‑quantitative reverse transcriptase‑polymerase chain reaction. One nano gram per millilitre of S. surattense leaf‑extract gave 115% glucose uptake on L6 myotubes. It also showed elevated levels of GLUT‑4 mRNA transcripts, when compared with control cells. Conclusion: These studies strongly support the anti‑diabetic nature of S. surattense.
RESUMO
Objective This study aims to investigate the effects of high-fat diet rich in perilla oil on the insulin sensitivity-related gene expression in skeletal muscle in insulin resistant rats.Methods The insulin resistant ( IR) rat models were randomly divided into 2 groups, including high fat group ( HF) and perilla oil ( PO) intervention group fed with 20%substitution of lard energy in the HF.The insulin sensitivity of rats was measured after 4 weeks.Theα-linolenic acid ( ALA) content of PO in the rat plasma were analyzed by gas chromatograph.Real-time PCR was applied to measure glucose transporter 4 ( GLUT4 ) and insulin receptor substrate-1 ( IRS-1 ) mRNA, and Western blot assay was used for detecting the expression of GLUT4 and IRS-1 in the skeletal muscle.Results At the gene and protein levels, PO remarkably reduced the level of IRS-1 and upregulated the level of GLUT4 with increasing intake of ALA and serum ALA content in IR rats.The results of hyperinsulinemic-euglycemic clamp test showed no significant difference between the two groups.Conclusions The results of our study suggest that consumption of n-3 PUFA at levels that can typically be found in the diet fed to IR rats in the form of ALA (0.556 g/d) may not improve insulin sensitivity, even though regulating the expression of GLUT4 and IRS-1 in the skeletal muscle.
RESUMO
Basic biochemical index were measured weekly in hyperuricemia rats.Real-time quantitative PCR technology was employed to measure glucose transporter-4 (GLUT-4),insulin receptor substrate (IRS)-1,and IRS-2 mRNA expression in the skeletal muscle and adipose tissue.The gene expression of GLUT-4 and IRS-2 are significantly lower in the last weeks of the hyperuricemia rat.Insulin resistance caused by hyperuricemia is probably related to the lowering expression levels of GLUT-4 and IRS-2 mRNA in the target tissues.
RESUMO
Exendin-4 (Ex-4), a glucagon-like peptide-1 receptor (GLP-1R) agonist, has been known to reverse hepatic steatosis in ob/ob mice. Although many studies have evaluated molecular targets of Ex-4, its mechanism of action on hepatic steatosis and fibrosis has not fully been determined. In the liver, glucose transporter 4 (GLUT4) is mainly expressed in hepatocytes, endothelial cells and hepatic stellate cells (HSCs). In the present study, the effects of Ex-4 on GLUT4 expression were determined in the liver of ob/ob mice. Ob/ob mice were treated with Ex-4 for 10 weeks. Serum metabolic parameters, hepatic triglyceride levels, and liver tissues were evaluated for hepatic steatosis. The weights of the whole body and liver in ob/ob mice were reduced by long-term Ex-4 treatment. Serum metabolic parameters, hepatic steatosis, and hepatic fibrosis in ob/ob mice were reduced by Ex-4. Particularly, Ex-4 improved hepatic steatosis by enhancing GLUT4 via GLP-1R activation in ob/ob mice. Ex-4 treatment also inhibited hepatic fibrosis by decreasing expression of connective tissue growth factor in HSCs of ob/ob mice. Our data suggest that GLP-1 agonists exert a protective effect on hepatic steatosis and fibrosis in obesity and type 2 diabetes.
Assuntos
Animais , Camundongos , Fator de Crescimento do Tecido Conjuntivo , Células Endoteliais , Fígado Gorduroso , Fibrose , Peptídeo 1 Semelhante ao Glucagon , Receptor do Peptídeo Semelhante ao Glucagon 1 , Proteínas Facilitadoras de Transporte de Glucose , Células Estreladas do Fígado , Hepatócitos , Fígado , Obesidade , Triglicerídeos , Pesos e MedidasRESUMO
Objective:To investigate the correlation between G protein-coupled receptor 120 ( GPR120 ) and glucose transporter 4 (GLUT4) in 3T3-L1 cells.Methods:3T3-l1 cells were induced for differentiation,GRP120 mRNA was detected by RT-PCR and Oil red O was used to determine fat expression.GPR120 expression was knocked down by a specific siRNA in 3T3-L1cells.3T3-L1 cell that were tranfected with GPR120 siRNA were incubated with palmitic acid for 24 hours.Then,real-time PCR and Western blot were used to detect the expression of GLUT4 mRNA and protein.Results: Induced differentiation led to GPR120 overexpression in 3T3-L1 cells ( P<0.05 ).GPR120 knockdown resulted in reduction of both lipid volume and number in 3T3-L1 cells.Furthermore,GPR120 knockdown decreased GLUT4 mRNA and protein levels in 3T3-L1 cells (P<0.05,respectively).Conclusion:GPR120 affects the expression level of GLUT4 in insulin signaling pathway,suggesting its involvement in the initiation of insulin resist-ance.
RESUMO
Objective To explore the effect of QizhiJiangtang Capsule on the insulin resistance (IR)in the diabetic rats,and to clarify the action mechanism.Methods The diabetes rat models were induced by high fat diet combined with STZ injection.The successful models of the rats were randomly divided into diabetes group (DM), ShenqiJiangtang Granule group (SQ)and high (QJH),middle-(QJM),low (QJL)doses of QizhiJiangtang Capsule groups;at the same time control group (NC)was established. The drug concentrations in high, middle and low-doses of QizhiJiangtang Capsules groups were 1.35, 0.68, and 0.34 g · kg-1 respectively;and the concentration of ShenqiJiangtang Granule was 0.27 g·kg-1.After the diabetic model was established successfully, the rats were treated for 8 weeks on the basis of drug dose.Then the levels of fasting blood glucose (FBG),fasting insulin (FINS),insulin resistance index (IRI)and biochemical indexes related to lipid metabolism of the rats were measured using blood glucose detector and automatic biochemistry analyser.The gene expression of insulin receptor substrate-1 (IRS-1),phosphatidyl inositol 3-kinase (PI3K),and glucose transporter 4 (GLUT4)in liver tissue were examined by Real Time PCR.The levels of tumor necrosis factorα(TNF-α)and adiponectin (ADPN)in serum were detected using ELISA.Results Compared with control group,the levels of FBG,FINS and IRI of the rats in diabetes group were significantly increased (P<0.05 or P<0.01 );the serum total cholesterol (TC), triglyceride (TG)and low density lipoprotein (LDL)levels were significantly increased (P<0.05 ), while the serum high-density lipoprotein (HDL)level was significantly decreased (P<0.05);the mRNA expression levels of IRS-1,PI3K and GLUT4 in liver tissue were decreased (P<0.05);the level of serum TNF-αwas increased (P<0.05),but the ADPN level was decreased (P<0.05).Compared with diabetes group,the FBG level and IRI of the rats in QizhiJiangtang Capsule and ShenqiJiangtang Granule groups were significantly decreased (P<0.01);the levels of FINS of the rats middle and high doses of in QizhiJiangtang Capsule groups and ShenqiJiangtang Granule group were significantly decreased (P<0.05);the levels of serum TC,TG and LDL of the rats in middle dose of QizhiJiangtang Capsule group and ShenqiJiangtang Granule group were significantly decreased (P<0.05 or P<0.01),but the HDL level was increased (P<0.05);the mRBA expression lvels of IRS-1,PI3K and GLUT4 inliver tissue were increased (P<0.05);the levels of serum TNF-αof the rats in middle dose of QizhiJiangtang Capsule group and Shenqijiangtang Granule group were significantly decreased (P<0.05),but the serum ADPN levels were increased (P<0.05 ). Conclusion QizhiJiangtang Capsule can significantly improve the IR in the diabetic rats,and the pharmacological mechanisms are related to adapting the blood lipid component and insulin signal transduction pathways.