Objective: To investigate the changes in glucose transporter-4(Glut-4) mRNA expression in skeletal muscle before and after the thoracic operation and to observe the changes in Glut-4 mRNA expression by preoperative in...Objective: To investigate the changes in glucose transporter-4(Glut-4) mRNA expression in skeletal muscle before and after the thoracic operation and to observe the changes in Glut-4 mRNA expression by preoperative infusion of glucose. Methods: Twelve cases of elective thoracic operation were randomly divided into two groups, namely ordinary group Ⅰ and glucose infusion group Ⅱ. One gram of intercostal muscle was taken while thorax being opened and closed from patients under general anesthesia. Total RNA of the muscle cells was extracted by TRIzol one-step assay. Reverse transcription-competitive polymerase chain reaction (RT-PCR) was used to determine the Glut-4 mRNA amplification products with β-actin mRNA as an internal control. The Glut-4 mRNA expression was expressed by targeted gene /β-actin ×100%. The plasma glucose and insulin levels were determined at the same time.Results: Glut-4 mRNA expression was significantly reduced(P<0.05) and plasma glucose level increased (P<0.05), while thorax was being closed as compared with those while being opened. However, Glut-4 mRNA expression in glucose infusion group Ⅱ was significantly higher than ordinary group Ⅰ (P<0.01) and plasma glucose level in group Ⅱ was lower than group Ⅰ(P<0.05) when thorax was being closed. Conclusion: The results indicate that the synthesis of Glut-4 is suppressed by the surgical stress of thoracic operation under general anesthesia. We found that preoperative infusion glucose can increase Glut-4 mRNA expression at the same surgical stress and relieve postoperative insulin resistance.展开更多
Triose phosphate translocator (TPT) is located in the inner membrane of plant chloroplasts. It catalyzes the counter exchange of those phosphate/3-phosphoglycerate and phosphate. To obtain the basic information on the...Triose phosphate translocator (TPT) is located in the inner membrane of plant chloroplasts. It catalyzes the counter exchange of those phosphate/3-phosphoglycerate and phosphate. To obtain the basic information on the structure-function relation, a cDNA encoding the complete precursor of the triose phosphate translocator has been isolated from wheat (Triticum aestivum L.) by RACE ( rapid amplification of cDNA ends) strategies. The wheat TPT cDNA encodes a precursor protein of 402 amino acid residues with a deduced molecular weight of 43 kD. A putative processing site between Ala-78 and Ala-79 of the precursor protein is suggested by comparison with those of the TPTs from spinach (Spinacia oleracea Mill.) and maize (Zea mays L.). The mature part of wheat TPT consists of 324 amino acid with a molecular weight of 35 kD, which share 89% identity with maize TPT. The amino acids Lys-274 and Arg-275 (mature protein) which is regarded as the substrate-binding site, are both conserved in plant TPTs. The gene expression analysis for leaves, coleoptiles, roots and seeds of wheat showed that the TPT transcript was only detectable in leaves and coleoptiles. No apparent expression signal was detected in the roots and seeds. This indicated that the expression of wheat TPT might be restricted to green tissues.展开更多
Caveolae and non-caveolar lipid rafts are two types of membrane lipid microdomains that play important roles in insulin-stimulated glucose uptake in adipocytes. In order to ascertain their specific functions in this p...Caveolae and non-caveolar lipid rafts are two types of membrane lipid microdomains that play important roles in insulin-stimulated glucose uptake in adipocytes. In order to ascertain their specific functions in this process, caveolae were ablated by caveolin-1 RNA interference. In Cav-1 RNAi adipocytes, neither insulin-stimulated glucose uptake nor Glut-4 (glucose transporter 4) translocation to membrane lipid microdomains was affected by the ablation of caveolae. With a modified sucrose density gradient, caveolae and non-caveolar lipid rafts could be separated. In the wild-type 3T3- L l adipocytes, Glut-4 was found to be translocated into both caveolae and non-caveolar lipid rafts. However, in Cav1 RNAi adipocytes, Glut-4 was localized predominantly in non-caveolar lipid rafts. After the removal of insulin, caveolaelocalized Glut-4 was internalized faster than non-caveolar lipid raft-associated Glut-4. The internalization of Glut-4 from plasma membrane was significantly decreased in Cav-1 RNAi adipocytes. These results suggest that insulin-stimulated Glut-4 translocation and glucose uptake are caveolae-independent events. Caveolae play a role in the internalization of Glut-4 from plasma membrane after the removal of insulin.展开更多
AIM:To evaluate the correlation between the level of 18 F-fluoro-2-deoxyglucose (18 F-FDG) uptake and glucose transporter 1 (GLUT1) expression in colorectal adenocarcinoma (CRA).METHODS:Forty four patients with resect...AIM:To evaluate the correlation between the level of 18 F-fluoro-2-deoxyglucose (18 F-FDG) uptake and glucose transporter 1 (GLUT1) expression in colorectal adenocarcinoma (CRA).METHODS:Forty four patients with resected CRA and preoperative 18 F-FDG positron emission tomography computed tomography data were investigated in this study.Comparison of maximum standardized uptake value (SUVmax) of the lesion was made with GLUT1 expression by immunohistochemistry and various clinicopathologic factors including tumor volume,invasion depth,gross finding,and lymph node metastasis.RESULTS:SUVmax was 14.45 ± 7.0 in negative GLUT1 expression cases,15.51 ± 5.7 in weak GLUT1 expression cases,and 16.52 ± 6.8 in strong GLUT1 expression cases,and there was no correlation between between GLUT1 expression and SUVmax.SUVmax was significantly correlated with tumor volume (P < 0.001).However,there was no significant differences in SUVmax and GLUT1 expression among other clinicopathologic factors.CONCLUSION:GLUT1 expression does not correlates significantly with 18 F-FDG uptake in CRA.18 F-FDG uptake was increased with tumor volume,which is statistically significant.展开更多
AIM: TO investigate the effects of the somatostatin analogue, octreotide, on maltose and sucrase activities and expression of glucose transporter type 2 (GLUT2) in obese rat intestinal mucosa. METHODS: We divided ...AIM: TO investigate the effects of the somatostatin analogue, octreotide, on maltose and sucrase activities and expression of glucose transporter type 2 (GLUT2) in obese rat intestinal mucosa. METHODS: We divided 49 Sprague-Dawley rats into a group of 31 high fat diet-induced obese rats and a group of 18 normal controls. The obese rats were separated into an octreotide treated group 9f 16 rats and an obese group of 15. The intervention (:jroup was injected with octreotide at 40 ±g/kg body weight every 12 h for 8 d. Rat body weight was measured weekly to calculate Lee's index. After euthanization, maltase and sucrase activities in the small intestine were measured by activity assays, and the fasting plasma glucose level was measured. The expression of GLUT2 in small intestinal mucosa was analyzed by immunohistochemistry, reverse transcriptase polymerase chain reaction and Western blotting assays. RESULTS: Body weight, Lee's index, fasting plasma glucose level, maltase activity in small intestinal mucosa, mucosa and apical GLUT2, GLUT2 mRNA and protein expression levels were all significantly higher in the obese group than in the normal control group (605.61 ± 141.00 vs 378.54 ±111.75, 337.61 ± 10.82 vs 318.73 ± 20.10, 8.60± 1.38 vs 7.33 ± 0.70, 156.01 ± 58.81 vs 50.43 ± 30.49, 390 744.2± 62 469.21 vs 170 546.50 ± 50 646.14, 26 740.18 ±3809.60 vs 354.98± 57.19, 0.26± 0.11 vs 0.07± 0.02, and 2.08 ± 0.59 vs 1.27 ± 0.38, respectively, all P 〈 0.01). Sucrase activity did not differ between the two groups. Octreotide intervention significantly decreased the body weight and fasting plasma glucose level of obese rats (508.27 ± 94.39 vs 605.61 ± 141.00, 7.58 ± 1.51 vs 8.60±1.38, respectively, all P 〈 0.05). The intestinal mucosa and apical GLUT2, expression of GLUT2 mRNA and protein were also significantly lower in the octreotide intervention group than in the obese group (269 975.2 ± 53 730.94 vs 390 744.2 ± 62 469.21, 3758.06 ± 364.51 vs 26 740.18 ± 3809.60, 0.08 ± 0.02 vs 0.26 ±0.11, and 1.31 ± 0.27 vs 2.08 ±0.59, respectively, all P 〈 0.01). CONCLUSION: High fat dietinduced obesity is associated with elevated intestinal maltase activity, GLUT2 expression, and permanent apical GLUT2 in the small intestinal mucosa of rats. Octreotide can inhibit these effects.展开更多
AIM:To investigate the role of glucose transporter 1 (GLUT1) expression in colorectal carcinogenesis and evaluate the correlation with clinicopathological parameters and apoptosis-activating factor-1 (Apaf-1) expressi...AIM:To investigate the role of glucose transporter 1 (GLUT1) expression in colorectal carcinogenesis and evaluate the correlation with clinicopathological parameters and apoptosis-activating factor-1 (Apaf-1) expression in colorectal adenocarcinomas. METHODS:We used tissue microarrays consisting of 26 normal mucosa,50 adenomas,515 adenocarcinomas,and 127 metastatic lesions. Medical records were reviewed and clinicopathological analysis was performed. RESULTS:GLUT1 expression was absent in normal mucosa and low or moderately apparent in 19 cases (38.0%) of 50 adenomas. However,GLUT1 expression was detected in 423 (82.1%) of 515 adenocarcinomas and in 96 (75.6%) of 127 metastatic lesions. GLUT1 expression was significantly correlated with female gender (P = 0.009),non-mucinous tumor type (P = 0.045),poorer differentiation (P = 0.001),lymph node metastasis (P < 0.001),higher AJCC and Dukes stage (P < 0.001 and P < 0.001,respectively). There was a significant inverse correlation between GLUT1 expression and Apaf-1 expression (P = 0.001). In univariate survival analysis,patients with GLUT1 expression demonstrated poor overall survival and disease-free survival (P = 0.047 and P = 0.021,respectively,log-rank test). CONCLUSION:GLUT1 expression was frequently increased in adenocarcinomas and metastatic lesions. GLUT1 expression was significantly correlated with poorer clinicopathologic phenotypes and survival of patients with colorectal adenocarcinomas.展开更多
The clinical implications of non-alcoholic fatty liver diseases(NAFLD)derive from their potential to progress to fibrosis and cirrhosis.Inappropriate dietary fat intake,excessive intake of soft drinks,insulin resistan...The clinical implications of non-alcoholic fatty liver diseases(NAFLD)derive from their potential to progress to fibrosis and cirrhosis.Inappropriate dietary fat intake,excessive intake of soft drinks,insulin resistance and increased oxidative stress results in increased free fatty acid delivery to the liver and increased hepatic triglyceride(TG)accumulation.An olive oil-rich diet decreases accumulation of TGs in the liver,improves postprandial TGs,glucose and glucagonlike peptide-1 responses in insulin-resistant subjects, and upregulates glucose transporter-2 expression in the liver.The principal mechanisms include:decreased nuclear factor-kappaB activation,decreased lowdensity lipoprotein oxidation,and improved insulin resistance by reduced production of inflammatory cytokines(tumor necrosis factor,interleukin-6)and improvement of jun N-terminal kinase-mediated phosphorylation of insulin receptor substrate-1.The beneficial effect of the Mediterranean diet is derived from monounsaturated fatty acids,mainly from olive oil.In this review,we describe the dietary sources of the monounsaturated fatty acids,the composition of olive oil,dietary fats and their relationship to insulin resistance and postprandial lipid and glucose responses in non-alcoholic steatohepatitis,clinical and experimental studies that assess the relationship between olive oil and NAFLD,and the mechanism by which olive oil ameliorates fatty liver,and we discuss future perspectives.展开更多
Sea cucumber and cordyceps sinensis are used as both food and traditional medicines in Asia. This study was carried out in order to investigate the hpyerglycemic effect of a mixture of sea cucumber (Apostichopusjapon...Sea cucumber and cordyceps sinensis are used as both food and traditional medicines in Asia. This study was carried out in order to investigate the hpyerglycemic effect of a mixture of sea cucumber (Apostichopusjaponicas) and cordyceps sinensis (Cor-dyceps militaris) (SCC) in diabetic rat and explore the mechanism underlining such an effect. The diabetic model rat was induced with intraperitoneal injection of streptozotocin (STZ). The diabetic model rats were randomly divided into control group (0.9% NaC1), low dose group (300 mg SCC.(kg body weight)-1) and high dose group (1200 mg SCC (kg body weight)-l). Sodium chloride and SCC were intragastrically administered once a day for 35 d. Changes in fasting serum glucose and serum insulin content, oral glucose tolerance and liver and muscle glycogen content were routinely evaluated. Pancreas tissue and β-cells of islets were observed under both optical and transmission electronic microscope, respectively. The abundance of glucose metabolism-relating genes in gastrocnemius and epididymal adipose tissue was determined with either reverse transcription PCR (RT-PCR) or western blotting. Results showed that SCC significantly decreased fasting serum glucose content, improved glucose tolerance and increased serum insulin and glycogen content; repaired STZ-injured β-cells of diabetic rat, and increased the expression of phosphatidylinositol 3 kinase (PI(3)K), protein kinase B (PKB) and glucose transporter 4 (Glut4) encoding protein in both gastroenemius and adipose tissue, and Glut4 encoding gene in peripheral tissue. Our findings demonstrated that SCC exerted an anti-hyperglycemic effect by repairing β-cells and promoting insulin-mediated signal transduction pathway in insulin-sensitive gastrocnemius and adipose tissue.展开更多
Glucose and other carbohydrates are transported into cells using members of a family of integral membrane glucose transporter (GLUT) molecules. To date 14 members of this family, also called the solute carrier 2A prot...Glucose and other carbohydrates are transported into cells using members of a family of integral membrane glucose transporter (GLUT) molecules. To date 14 members of this family, also called the solute carrier 2A proteins have been identified which are divided on the basis of transport characteristics and sequence similarities into several families (Classes 1 to 3). The expression of these different receptor subtypes varies between different species, tissues and cellular subtypes and each has differential sensitivities to stimuli such as insulin. The liver is a contributor to metabolic carbohydrate homeostasis and is a major site for synthesis, storage and redistribution of carbohydrates. Situations in which the balance of glucose homeostasis is upset such as diabetes or the metabolic syndrome can lead metabolic disturbances that drive chronic organ damage and failure, confirming the importance of understanding the molecular regulation of hepatic glucose homeostasis. There is a considerable literature describing the expression and function of receptors that regulate glucose uptake and release by hepatocytes, the most import cells in glucose regulation and glycogen storage. However there is less appreciation of the roles of GLUTs expressed by non parenchymal cell types within the liver, all of which require carbohydrate to function. A better understanding of the detailed cellular distribution of GLUTs in human liver tissue may shed light on mechanisms underlying disease pathogenesis. This review summarises the available literature on hepatocellular expression of GLUTs in health and disease and highlights areas where further investigation is required.展开更多
The authors described a novel submerged batch culture system that produced high levels of amylase by Aspergillus kawachii using whole barley (WB), the surface of which is covered by its husk. In this study, detailed...The authors described a novel submerged batch culture system that produced high levels of amylase by Aspergillus kawachii using whole barley (WB), the surface of which is covered by its husk. In this study, detailed analyses determining the amylase activities, residual sugars, fungal morphology and expression levels of genes were performed in a submerged culture using WB to address the mechanism underlying high amylase productivity in A. kawachii. High levels of glucoamylase and acid-stable u-amylase were produced in this culture, and expression levels of amylases, as well as glucose-repressive genes including high-affinity glucose transporter and peroxidase/catalase were also high. On the other hand, the morphology of mycelia was altered, with swollen, bulbous, multi-septum hyphae and conidiophores that normally form in a solid culture being partially generated. Furthermore, cell cycle and post-translational modification-related gene expression levels were altered, and were similar to those in the solid culture. These findings suggest that high amylase productivity in the submerged culture using WB is accompanied by both the up-regulation of amylase genes and activation of post-translational modifications due to fungal morphological changes being brought closer to those in the solid culture.展开更多
The hexoses glucose, galactose and fructose serve as important dietary energy sources in animals and glucose plays a central role in energy homeostasis within eucaryotic cells. As relatively little is known about patt...The hexoses glucose, galactose and fructose serve as important dietary energy sources in animals and glucose plays a central role in energy homeostasis within eucaryotic cells. As relatively little is known about patterns of hexose transporters expression in birds gastrointestinal tract, the aim of the study was to examine glucose transporters 2 (GLUT-2) and glucose transporters 5 (GLUT-5) expression in stomach and duodenal epithelium of two different species--broilers (Gallus gallus domesticus) and ostriches (Struthio camelus var. domesticus) chicken. Materials from the two parts of gastrointestinal tract were collected from six 7-day-old female broilers and six 7-day-old female ostriches. Specimens were fixed with 10% formalin, embedded into paraffin, cut into 7 lain thick slices, followed by immunohistochemical staining with polyclonal primary antibodies rabbit anti-GLUT-2 and rabbit anti-GLUT-5; the staining was carried out according to the manufacturers guidelines (IHC kit, Abcam, UK). The investigation showed that the staining for both antibodies was more intensive in the epithelial cells of stomach and duodenum of the 7-day-old broilers. In duodenal epithelium, goblet cells and brush border membranes were stained in both species, however the signal was stronger for GLUT-5 than GLUT-2. Staining for GLUT-2 and GLUT-5 occurred in different parts of gastrointestinal tract of 7-day-old ostriches, but was weaker compared to 7-day-old broilers, which showed that the gastrointestinal tract of 7-day-old female broilers was more developed for transportation ofhexoses than 7-day-old female ostriches.展开更多
AIM: To test whether oral L-81 treatment could im-prove the condition of mice with diabetes and to investigate how L-81 regulates microsomal triglyceride transfer protein (MTP) activity in the liver. METHODS: Genetica...AIM: To test whether oral L-81 treatment could im-prove the condition of mice with diabetes and to investigate how L-81 regulates microsomal triglyceride transfer protein (MTP) activity in the liver. METHODS: Genetically diabetic (db/db) mice were fed on chow supplemented with or without L-81 for 4 wk. The body weight, plasma glucose level, plasma lipid profile, and adipocyte volume of the db/db mice were assessed after treatment. Toxicity of L-81 was also evaluated. To understand the molecular mecha-nism, HepG2 cells were treated with L-81 and the effects on apolipoprotein B (apoB) secretion and mRNA level of the MTP gene were assessed.RESULTS: Treatment of db/db mice with L-81 sig-nificantly reduced and nearly normalized their body weight, hyperphagia and polydipsia. L-81 also markedly decreased the fasting plasma glucose level, improved glucose tolerance, and attenuated the elevated levels of plasma cholesterol and triglyceride. At the effective dosage, little toxicity was observed. Treatment of HepG2 cells with L-81 not only inhibited apoB secretion, but also signif icantly decreased the mRNA level of the MTP gene. Similar to the action of insulin, L-81 exerted its effect on the MTP promoter. CONCLUSION: L-81 represents a promising candidate in the development of a selective insulin-mimetic mol-ecule and an anti-diabetic agent.展开更多
In this study, Computational Fluid Dynamics(CFD) is used to investigate and compare the impact of bioreactor parameters(such as its geometry, medium flow-rate, scaffold configuration) on the local transport phenomena ...In this study, Computational Fluid Dynamics(CFD) is used to investigate and compare the impact of bioreactor parameters(such as its geometry, medium flow-rate, scaffold configuration) on the local transport phenomena and, hence, their impact on human mesenchymal stem cell(hM SC) expansion. The geometric characteristics of the TissueFlex174;(Zyoxel Limited, Oxford, UK) microbioreactor were considered to set up a virtual bioreactor containing alginate(in both slab and bead configuration) scaffolds. The bioreactor and scaffolds were seeded with cells that were modelled as glucose consuming entities. The widely used glucose medium, Dulbecco's Modified Eagle Medium(DMEM), supplied at two inlet flow rates of 25 and 100 μl·h^(-1), was modelled as the fluid phase inside the bioreactors. The investigation, based on applying dimensional analysis to this problem, as well as on detailed three-dimensional transient CFD results, revealed that the default bioreactor design and boundary conditions led to internal and external glucose transport, as well as shear stresses, that are conducive to h MSC growth and expansion. Furthermore, results indicated that the ‘top-inout' design(as opposed to its symmetric counterpart) led to higher shear stress for the same media inlet rate(25 μl·h^(-1)), a feature that can be easily exploited to induce shear-dependent differentiation. These findings further confirm the suitability of CFD as a robust design tool.展开更多
OBJECTIVE: To investigate the effect of Yiqihuoxue prescription(YQHX) from Traditional Chinese Medicine(TCM) on myocardial glucose and lipid metabolism after myocardial infarction via the cross talk between the liver ...OBJECTIVE: To investigate the effect of Yiqihuoxue prescription(YQHX) from Traditional Chinese Medicine(TCM) on myocardial glucose and lipid metabolism after myocardial infarction via the cross talk between the liver kinase B1(LKB1)-dependent Notch1 and adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK). YQHX was prepared with substances with properties that benefit, to activate blood circulation based on the TCM theory.METHODS: Animal models of myocardial infarction were established by ligating Sprague Dawley rats' left anterior descending coronary arteries. The animals were randomly divided into a myocardial infarction(MI) group, a YQHX group, a perindopril group, a γ-secretase inhibitor, Notch signal inhibitor(DAPT) group, a DAPT+YQHX group and a sham group. The related drugs were administered on the second day after operation, and changes in the relevant indexes were examined on weeks 1 and 4.Changes in cardiac structure and function were examined by echocardiography. The glucose and free fatty acids(FFA) were examined by ELISA. The expression of Notch, LKB1 and AMPK m RNA was examined by a real-time fluorescence quantitative method. The expression of glucose transporter 4(GLUT4), and the expression of total acetyl-Co A carboxylase(ACC) and its phosphorylation were examined by western blotting.RESULTS: Compared with the sham group, the expression of Notch, LKB1 and AMPK m RNA in the MI group was lower. Compared with the MI group, the expression of these m RNAs in the YQHX and perindopril groups was higher, and their expression in the DAPT group was lower. At all time points, the protein expression of GLUT4 and p ACC decreased in the MI group. On week 1, the expression of p ACC protein was higher. In the DAPT group, the expression of p ACC protein decreased. Compared with the YQHX group, the expression of p ACC protein in the DAPT + YQHX group was lower. On week 4,compared with the MI group, the expression of GLUT4 protein in the YQHX group and the perindo-pril group was higher. The expression of GLUT4 protein in the DAPT group decreased. Compared with the YQHX group, the expression of GLUT4 protein in the DAPT+YQHX group was lower. There was no significant difference in the expression of ACC protein between the groups.CONCLUSION: YQHX promoted cross talk between the LKB1-dependent Notch1 and AMPK in myocardial tissue after myocardial infarction. Furthermore,it regulated the glucose and lipid metabolism of cardiomyocytes at different time points, thereby ameliorating the cardiac energy metabolism via different mechanisms and protecting the heart.展开更多
OBJECTIVE: To investigate the effect of low frequency electro-pulse acupuncture(EA) on blood glucose in rats with streptozotocin-induced type 2diabetes, and the possible mechanism underlying the action.METHODS: Rat mo...OBJECTIVE: To investigate the effect of low frequency electro-pulse acupuncture(EA) on blood glucose in rats with streptozotocin-induced type 2diabetes, and the possible mechanism underlying the action.METHODS: Rat models were established with high fat feeding and intraperitoneal injection of streptozotocin(STZ)(30 mg/kg). Rats with a random blood glucose > 16.7 mmol/L and blood glucose at 2 h-point of oral glucose tolerance test(OGTT) > 11.1 mmol/L were included as diabetic rats, and randomly divided into model group, EA Weiwanxiashu(EX-B 3) group, EA Zusanli(ST 36)group, glimepiride group, and EA non-acupoint group(n = 12). EA(2 Hz continuous wave, 2 m A,20 min/day, 6 days/week, 4 weeks) and intra-gastric administration of glimepiride were applied as interventions. With fasting blood glucose and OGTT tested at the end of the intervention, thestudy observed the patterns of hypoglycemic effects. For mechanism study, it observes hematoxylin and eosin staining and Masson staining of pancreas paraffin sections, protein expression of glucagon-like peptide 1 receptor(GLP-1R) in the pancreas and skeletal muscle, glucose transporter 4(GLUT4) protein expression in skeletal muscle membrane, to detect whether EA controls blood glucose via regulation of GLP-1R.RESULTS: EA Weiwanxiashu(EX-B 3) significantly increased model rats' pancreas GLP-1R, and GLUT4 of skeletal muscle membrane; the therapy significantly decreased model rats' skeletal muscle GLP-1R, restored pancreas morphology, and reduced fasting blood glucose and insulin resistance indices.CONCLUSION: EA Weiwanxiashu(EX-B 3) alone has significant effect on glycemia. EA Weiwanxiashu(EX-B 3) plus glimepiride further strengthen the effect. The regulation of the GLP-1R in pancreas and skeletal muscle might be mechanism underpinning the effect.展开更多
Most of antieancer agents can not be used for treatment of brain glioma due to the existence of the blood brain barrier (BBB). The over-expression of glucose transporters (GLUTs) on the BBB and brain glioma cells ...Most of antieancer agents can not be used for treatment of brain glioma due to the existence of the blood brain barrier (BBB). The over-expression of glucose transporters (GLUTs) on the BBB and brain glioma cells enables the possibility that the GLUTs ligand modified drug carrier transports across the BBB, and targets to the brain glioma cells. The objectives of the present study were to synthesize a new glucose conjugate material, TPGS1000-Glu, develop a kind of TPGSI00o-Glu modified epirubicin liposomes, and evaluate their efficacy. The studies were performed on the BBB co-culture model and brain glioma cells in vitro. TPGS 1000-Glu was synthesized by conjugating TPGSlo00_COOH with 4-aminophenyl-[3-D-glucopyranoside (Glu), and confirmed by MALDI-TOF-MS spectrum. TPGS^0oo-GIu modified epirubicin liposomes were prepared with a high drug encapsulation efficiency (〉97%), a nanosize (approximately 90 nm), and a minimal drug leakage in fetal bovine serum (FBS)-containing buffer system. The BBB co-culture model was established, and after applying TPGSl0oo-Glu modified epirubicin liposomes to the model, transport of liposomal drug across the BBB was evidenced. Besides, TPGS1000-Glu modified epirubicin liposomes showed the strongest cellular drug uptake and anti-glioma efficacy after transport across the BBB in vitro. The synthesized TPGS1000-Glu material could offer a new targeting ligand for the BBB, while the developed TPGS1000-Glu modified epirubicin liposomes might provide a potential anticancer formulation for treatment of brain glioma.展开更多
Canagliflozin(CANA)is a sodium-glucose co-transporter 2 inhibitor.One of the important mechanisms of CANA is the inhibitory effect on the glucose uptake in the proximal tubule of the nephron,and the other mechanism ca...Canagliflozin(CANA)is a sodium-glucose co-transporter 2 inhibitor.One of the important mechanisms of CANA is the inhibitory effect on the glucose uptake in the proximal tubule of the nephron,and the other mechanism can be the reduction of inflammatory cytokine expression monocytes and macrophages.It is proved by FDA for the management of type 2 diabetes.In the present work,we summarized the publication and clinical evidence of the CANA on healthy individuals and those with related metabolic diseases,such as type 1 and 2 diabetes,obesity,or cardiovascular and kidney diseases.This drug has been reported to offer potential advantages in regulating body weight and reducing heart failure,hypoglycemia,and stroke risk in patients with type 2 diabetes.Some in vitro and animal experiments also show that this drug has good effects on cancer treatment.However,some case reports and experiments also show the side effect of CANA,such as amputation,fracture,and pancreatitis,while the mechanism is still unknown.Overall,CANA has a good effect on the management of type 2 diabetes by reducing the risk of kidney failure,cardiovascular diseases,and stroke.However,as a new drug,more clinical trials and experiments of CANA should be carried out in the future.展开更多
Objective To evaluate the role of glucose transporter 1 (GLUT1) in the glucose uptake of glomerular mesangial cells.Methods Cultured human glomerular mesangial cells were used. The expressions of glucose transporter...Objective To evaluate the role of glucose transporter 1 (GLUT1) in the glucose uptake of glomerular mesangial cells.Methods Cultured human glomerular mesangial cells were used. The expressions of glucose transporter 1 mRNA and protein were detected with reverse transcription-polymerase chain reaction (RT-PCR), flow cytometry and immunofluorescence staining. Glucose uptake was determined with 2-deoxy-[3H]-D-glucose uptake assay.Results The expressions of GLUT1 mRNA and proteins were detected in human mesangial cells. Glucose uptake and its kinetics assay showed that GLUT1 is a functional glucose transporter in cultured human mesangial cells, and that its function could be inhibited by the specific inhibitor, Phloretin. Conclusion GLUT1 is the predominant glucose transporter in human mesangial cells, which has the kinetic characteristics of high affinity and low capacity for D-glucose. This suggests that in order for mesangial cells to take up excessive quantities of glucose, as in diabetes, changes in glucose transporter expression, translocation or activity may be required.展开更多
文摘Objective: To investigate the changes in glucose transporter-4(Glut-4) mRNA expression in skeletal muscle before and after the thoracic operation and to observe the changes in Glut-4 mRNA expression by preoperative infusion of glucose. Methods: Twelve cases of elective thoracic operation were randomly divided into two groups, namely ordinary group Ⅰ and glucose infusion group Ⅱ. One gram of intercostal muscle was taken while thorax being opened and closed from patients under general anesthesia. Total RNA of the muscle cells was extracted by TRIzol one-step assay. Reverse transcription-competitive polymerase chain reaction (RT-PCR) was used to determine the Glut-4 mRNA amplification products with β-actin mRNA as an internal control. The Glut-4 mRNA expression was expressed by targeted gene /β-actin ×100%. The plasma glucose and insulin levels were determined at the same time.Results: Glut-4 mRNA expression was significantly reduced(P<0.05) and plasma glucose level increased (P<0.05), while thorax was being closed as compared with those while being opened. However, Glut-4 mRNA expression in glucose infusion group Ⅱ was significantly higher than ordinary group Ⅰ (P<0.01) and plasma glucose level in group Ⅱ was lower than group Ⅰ(P<0.05) when thorax was being closed. Conclusion: The results indicate that the synthesis of Glut-4 is suppressed by the surgical stress of thoracic operation under general anesthesia. We found that preoperative infusion glucose can increase Glut-4 mRNA expression at the same surgical stress and relieve postoperative insulin resistance.
文摘Triose phosphate translocator (TPT) is located in the inner membrane of plant chloroplasts. It catalyzes the counter exchange of those phosphate/3-phosphoglycerate and phosphate. To obtain the basic information on the structure-function relation, a cDNA encoding the complete precursor of the triose phosphate translocator has been isolated from wheat (Triticum aestivum L.) by RACE ( rapid amplification of cDNA ends) strategies. The wheat TPT cDNA encodes a precursor protein of 402 amino acid residues with a deduced molecular weight of 43 kD. A putative processing site between Ala-78 and Ala-79 of the precursor protein is suggested by comparison with those of the TPTs from spinach (Spinacia oleracea Mill.) and maize (Zea mays L.). The mature part of wheat TPT consists of 324 amino acid with a molecular weight of 35 kD, which share 89% identity with maize TPT. The amino acids Lys-274 and Arg-275 (mature protein) which is regarded as the substrate-binding site, are both conserved in plant TPTs. The gene expression analysis for leaves, coleoptiles, roots and seeds of wheat showed that the TPT transcript was only detectable in leaves and coleoptiles. No apparent expression signal was detected in the roots and seeds. This indicated that the expression of wheat TPT might be restricted to green tissues.
文摘Caveolae and non-caveolar lipid rafts are two types of membrane lipid microdomains that play important roles in insulin-stimulated glucose uptake in adipocytes. In order to ascertain their specific functions in this process, caveolae were ablated by caveolin-1 RNA interference. In Cav-1 RNAi adipocytes, neither insulin-stimulated glucose uptake nor Glut-4 (glucose transporter 4) translocation to membrane lipid microdomains was affected by the ablation of caveolae. With a modified sucrose density gradient, caveolae and non-caveolar lipid rafts could be separated. In the wild-type 3T3- L l adipocytes, Glut-4 was found to be translocated into both caveolae and non-caveolar lipid rafts. However, in Cav1 RNAi adipocytes, Glut-4 was localized predominantly in non-caveolar lipid rafts. After the removal of insulin, caveolaelocalized Glut-4 was internalized faster than non-caveolar lipid raft-associated Glut-4. The internalization of Glut-4 from plasma membrane was significantly decreased in Cav-1 RNAi adipocytes. These results suggest that insulin-stimulated Glut-4 translocation and glucose uptake are caveolae-independent events. Caveolae play a role in the internalization of Glut-4 from plasma membrane after the removal of insulin.
基金Supported by National Research Foundation of Korea Grant funded by the Ministry of Education,Science and Technology through the Research Center for Resistant Cells,No.R13-2003-009
文摘AIM:To evaluate the correlation between the level of 18 F-fluoro-2-deoxyglucose (18 F-FDG) uptake and glucose transporter 1 (GLUT1) expression in colorectal adenocarcinoma (CRA).METHODS:Forty four patients with resected CRA and preoperative 18 F-FDG positron emission tomography computed tomography data were investigated in this study.Comparison of maximum standardized uptake value (SUVmax) of the lesion was made with GLUT1 expression by immunohistochemistry and various clinicopathologic factors including tumor volume,invasion depth,gross finding,and lymph node metastasis.RESULTS:SUVmax was 14.45 ± 7.0 in negative GLUT1 expression cases,15.51 ± 5.7 in weak GLUT1 expression cases,and 16.52 ± 6.8 in strong GLUT1 expression cases,and there was no correlation between between GLUT1 expression and SUVmax.SUVmax was significantly correlated with tumor volume (P < 0.001).However,there was no significant differences in SUVmax and GLUT1 expression among other clinicopathologic factors.CONCLUSION:GLUT1 expression does not correlates significantly with 18 F-FDG uptake in CRA.18 F-FDG uptake was increased with tumor volume,which is statistically significant.
基金Supported by Grants from the National Natural Sciences Foundation of China,No.30870919Sichuan Provincial Department of Science and Technology,No.2010SZ0176
文摘AIM: TO investigate the effects of the somatostatin analogue, octreotide, on maltose and sucrase activities and expression of glucose transporter type 2 (GLUT2) in obese rat intestinal mucosa. METHODS: We divided 49 Sprague-Dawley rats into a group of 31 high fat diet-induced obese rats and a group of 18 normal controls. The obese rats were separated into an octreotide treated group 9f 16 rats and an obese group of 15. The intervention (:jroup was injected with octreotide at 40 ±g/kg body weight every 12 h for 8 d. Rat body weight was measured weekly to calculate Lee's index. After euthanization, maltase and sucrase activities in the small intestine were measured by activity assays, and the fasting plasma glucose level was measured. The expression of GLUT2 in small intestinal mucosa was analyzed by immunohistochemistry, reverse transcriptase polymerase chain reaction and Western blotting assays. RESULTS: Body weight, Lee's index, fasting plasma glucose level, maltase activity in small intestinal mucosa, mucosa and apical GLUT2, GLUT2 mRNA and protein expression levels were all significantly higher in the obese group than in the normal control group (605.61 ± 141.00 vs 378.54 ±111.75, 337.61 ± 10.82 vs 318.73 ± 20.10, 8.60± 1.38 vs 7.33 ± 0.70, 156.01 ± 58.81 vs 50.43 ± 30.49, 390 744.2± 62 469.21 vs 170 546.50 ± 50 646.14, 26 740.18 ±3809.60 vs 354.98± 57.19, 0.26± 0.11 vs 0.07± 0.02, and 2.08 ± 0.59 vs 1.27 ± 0.38, respectively, all P 〈 0.01). Sucrase activity did not differ between the two groups. Octreotide intervention significantly decreased the body weight and fasting plasma glucose level of obese rats (508.27 ± 94.39 vs 605.61 ± 141.00, 7.58 ± 1.51 vs 8.60±1.38, respectively, all P 〈 0.05). The intestinal mucosa and apical GLUT2, expression of GLUT2 mRNA and protein were also significantly lower in the octreotide intervention group than in the obese group (269 975.2 ± 53 730.94 vs 390 744.2 ± 62 469.21, 3758.06 ± 364.51 vs 26 740.18 ± 3809.60, 0.08 ± 0.02 vs 0.26 ±0.11, and 1.31 ± 0.27 vs 2.08 ±0.59, respectively, all P 〈 0.01). CONCLUSION: High fat dietinduced obesity is associated with elevated intestinal maltase activity, GLUT2 expression, and permanent apical GLUT2 in the small intestinal mucosa of rats. Octreotide can inhibit these effects.
基金Supported by The Research Fund of Hanyang University (HY-2010-MC) to Paik SS
文摘AIM:To investigate the role of glucose transporter 1 (GLUT1) expression in colorectal carcinogenesis and evaluate the correlation with clinicopathological parameters and apoptosis-activating factor-1 (Apaf-1) expression in colorectal adenocarcinomas. METHODS:We used tissue microarrays consisting of 26 normal mucosa,50 adenomas,515 adenocarcinomas,and 127 metastatic lesions. Medical records were reviewed and clinicopathological analysis was performed. RESULTS:GLUT1 expression was absent in normal mucosa and low or moderately apparent in 19 cases (38.0%) of 50 adenomas. However,GLUT1 expression was detected in 423 (82.1%) of 515 adenocarcinomas and in 96 (75.6%) of 127 metastatic lesions. GLUT1 expression was significantly correlated with female gender (P = 0.009),non-mucinous tumor type (P = 0.045),poorer differentiation (P = 0.001),lymph node metastasis (P < 0.001),higher AJCC and Dukes stage (P < 0.001 and P < 0.001,respectively). There was a significant inverse correlation between GLUT1 expression and Apaf-1 expression (P = 0.001). In univariate survival analysis,patients with GLUT1 expression demonstrated poor overall survival and disease-free survival (P = 0.047 and P = 0.021,respectively,log-rank test). CONCLUSION:GLUT1 expression was frequently increased in adenocarcinomas and metastatic lesions. GLUT1 expression was significantly correlated with poorer clinicopathologic phenotypes and survival of patients with colorectal adenocarcinomas.
文摘The clinical implications of non-alcoholic fatty liver diseases(NAFLD)derive from their potential to progress to fibrosis and cirrhosis.Inappropriate dietary fat intake,excessive intake of soft drinks,insulin resistance and increased oxidative stress results in increased free fatty acid delivery to the liver and increased hepatic triglyceride(TG)accumulation.An olive oil-rich diet decreases accumulation of TGs in the liver,improves postprandial TGs,glucose and glucagonlike peptide-1 responses in insulin-resistant subjects, and upregulates glucose transporter-2 expression in the liver.The principal mechanisms include:decreased nuclear factor-kappaB activation,decreased lowdensity lipoprotein oxidation,and improved insulin resistance by reduced production of inflammatory cytokines(tumor necrosis factor,interleukin-6)and improvement of jun N-terminal kinase-mediated phosphorylation of insulin receptor substrate-1.The beneficial effect of the Mediterranean diet is derived from monounsaturated fatty acids,mainly from olive oil.In this review,we describe the dietary sources of the monounsaturated fatty acids,the composition of olive oil,dietary fats and their relationship to insulin resistance and postprandial lipid and glucose responses in non-alcoholic steatohepatitis,clinical and experimental studies that assess the relationship between olive oil and NAFLD,and the mechanism by which olive oil ameliorates fatty liver,and we discuss future perspectives.
基金supported by National Marine Public Welfare Scientific Research Project of China (No.201105029)the National Key Technology S&D Program (No.2012BAD33B07)Program for Changjiang Scholars and Innovative Research Team in University (IRT1188)
文摘Sea cucumber and cordyceps sinensis are used as both food and traditional medicines in Asia. This study was carried out in order to investigate the hpyerglycemic effect of a mixture of sea cucumber (Apostichopusjaponicas) and cordyceps sinensis (Cor-dyceps militaris) (SCC) in diabetic rat and explore the mechanism underlining such an effect. The diabetic model rat was induced with intraperitoneal injection of streptozotocin (STZ). The diabetic model rats were randomly divided into control group (0.9% NaC1), low dose group (300 mg SCC.(kg body weight)-1) and high dose group (1200 mg SCC (kg body weight)-l). Sodium chloride and SCC were intragastrically administered once a day for 35 d. Changes in fasting serum glucose and serum insulin content, oral glucose tolerance and liver and muscle glycogen content were routinely evaluated. Pancreas tissue and β-cells of islets were observed under both optical and transmission electronic microscope, respectively. The abundance of glucose metabolism-relating genes in gastrocnemius and epididymal adipose tissue was determined with either reverse transcription PCR (RT-PCR) or western blotting. Results showed that SCC significantly decreased fasting serum glucose content, improved glucose tolerance and increased serum insulin and glycogen content; repaired STZ-injured β-cells of diabetic rat, and increased the expression of phosphatidylinositol 3 kinase (PI(3)K), protein kinase B (PKB) and glucose transporter 4 (Glut4) encoding protein in both gastroenemius and adipose tissue, and Glut4 encoding gene in peripheral tissue. Our findings demonstrated that SCC exerted an anti-hyperglycemic effect by repairing β-cells and promoting insulin-mediated signal transduction pathway in insulin-sensitive gastrocnemius and adipose tissue.
文摘Glucose and other carbohydrates are transported into cells using members of a family of integral membrane glucose transporter (GLUT) molecules. To date 14 members of this family, also called the solute carrier 2A proteins have been identified which are divided on the basis of transport characteristics and sequence similarities into several families (Classes 1 to 3). The expression of these different receptor subtypes varies between different species, tissues and cellular subtypes and each has differential sensitivities to stimuli such as insulin. The liver is a contributor to metabolic carbohydrate homeostasis and is a major site for synthesis, storage and redistribution of carbohydrates. Situations in which the balance of glucose homeostasis is upset such as diabetes or the metabolic syndrome can lead metabolic disturbances that drive chronic organ damage and failure, confirming the importance of understanding the molecular regulation of hepatic glucose homeostasis. There is a considerable literature describing the expression and function of receptors that regulate glucose uptake and release by hepatocytes, the most import cells in glucose regulation and glycogen storage. However there is less appreciation of the roles of GLUTs expressed by non parenchymal cell types within the liver, all of which require carbohydrate to function. A better understanding of the detailed cellular distribution of GLUTs in human liver tissue may shed light on mechanisms underlying disease pathogenesis. This review summarises the available literature on hepatocellular expression of GLUTs in health and disease and highlights areas where further investigation is required.
文摘The authors described a novel submerged batch culture system that produced high levels of amylase by Aspergillus kawachii using whole barley (WB), the surface of which is covered by its husk. In this study, detailed analyses determining the amylase activities, residual sugars, fungal morphology and expression levels of genes were performed in a submerged culture using WB to address the mechanism underlying high amylase productivity in A. kawachii. High levels of glucoamylase and acid-stable u-amylase were produced in this culture, and expression levels of amylases, as well as glucose-repressive genes including high-affinity glucose transporter and peroxidase/catalase were also high. On the other hand, the morphology of mycelia was altered, with swollen, bulbous, multi-septum hyphae and conidiophores that normally form in a solid culture being partially generated. Furthermore, cell cycle and post-translational modification-related gene expression levels were altered, and were similar to those in the solid culture. These findings suggest that high amylase productivity in the submerged culture using WB is accompanied by both the up-regulation of amylase genes and activation of post-translational modifications due to fungal morphological changes being brought closer to those in the solid culture.
文摘The hexoses glucose, galactose and fructose serve as important dietary energy sources in animals and glucose plays a central role in energy homeostasis within eucaryotic cells. As relatively little is known about patterns of hexose transporters expression in birds gastrointestinal tract, the aim of the study was to examine glucose transporters 2 (GLUT-2) and glucose transporters 5 (GLUT-5) expression in stomach and duodenal epithelium of two different species--broilers (Gallus gallus domesticus) and ostriches (Struthio camelus var. domesticus) chicken. Materials from the two parts of gastrointestinal tract were collected from six 7-day-old female broilers and six 7-day-old female ostriches. Specimens were fixed with 10% formalin, embedded into paraffin, cut into 7 lain thick slices, followed by immunohistochemical staining with polyclonal primary antibodies rabbit anti-GLUT-2 and rabbit anti-GLUT-5; the staining was carried out according to the manufacturers guidelines (IHC kit, Abcam, UK). The investigation showed that the staining for both antibodies was more intensive in the epithelial cells of stomach and duodenum of the 7-day-old broilers. In duodenal epithelium, goblet cells and brush border membranes were stained in both species, however the signal was stronger for GLUT-5 than GLUT-2. Staining for GLUT-2 and GLUT-5 occurred in different parts of gastrointestinal tract of 7-day-old ostriches, but was weaker compared to 7-day-old broilers, which showed that the gastrointestinal tract of 7-day-old female broilers was more developed for transportation ofhexoses than 7-day-old female ostriches.
基金Supported by The Area of Excellence scheme of University Grants Committeethe Research Grant Council Grant, HKU 7642/05M to MCL, from Hong Kong
文摘AIM: To test whether oral L-81 treatment could im-prove the condition of mice with diabetes and to investigate how L-81 regulates microsomal triglyceride transfer protein (MTP) activity in the liver. METHODS: Genetically diabetic (db/db) mice were fed on chow supplemented with or without L-81 for 4 wk. The body weight, plasma glucose level, plasma lipid profile, and adipocyte volume of the db/db mice were assessed after treatment. Toxicity of L-81 was also evaluated. To understand the molecular mecha-nism, HepG2 cells were treated with L-81 and the effects on apolipoprotein B (apoB) secretion and mRNA level of the MTP gene were assessed.RESULTS: Treatment of db/db mice with L-81 sig-nificantly reduced and nearly normalized their body weight, hyperphagia and polydipsia. L-81 also markedly decreased the fasting plasma glucose level, improved glucose tolerance, and attenuated the elevated levels of plasma cholesterol and triglyceride. At the effective dosage, little toxicity was observed. Treatment of HepG2 cells with L-81 not only inhibited apoB secretion, but also signif icantly decreased the mRNA level of the MTP gene. Similar to the action of insulin, L-81 exerted its effect on the MTP promoter. CONCLUSION: L-81 represents a promising candidate in the development of a selective insulin-mimetic mol-ecule and an anti-diabetic agent.
基金Department of Engineering Science, University of Oxford, Scholarship
文摘In this study, Computational Fluid Dynamics(CFD) is used to investigate and compare the impact of bioreactor parameters(such as its geometry, medium flow-rate, scaffold configuration) on the local transport phenomena and, hence, their impact on human mesenchymal stem cell(hM SC) expansion. The geometric characteristics of the TissueFlex174;(Zyoxel Limited, Oxford, UK) microbioreactor were considered to set up a virtual bioreactor containing alginate(in both slab and bead configuration) scaffolds. The bioreactor and scaffolds were seeded with cells that were modelled as glucose consuming entities. The widely used glucose medium, Dulbecco's Modified Eagle Medium(DMEM), supplied at two inlet flow rates of 25 and 100 μl·h^(-1), was modelled as the fluid phase inside the bioreactors. The investigation, based on applying dimensional analysis to this problem, as well as on detailed three-dimensional transient CFD results, revealed that the default bioreactor design and boundary conditions led to internal and external glucose transport, as well as shear stresses, that are conducive to h MSC growth and expansion. Furthermore, results indicated that the ‘top-inout' design(as opposed to its symmetric counterpart) led to higher shear stress for the same media inlet rate(25 μl·h^(-1)), a feature that can be easily exploited to induce shear-dependent differentiation. These findings further confirm the suitability of CFD as a robust design tool.
基金Supported by the National Natural Science Foundation of China:Study of Influence of Supplementing Qi and Activating Blood Circulation Herbs on Microvascular Dysfunction and Related Regulators of Myocardial Infarction Rats(No.81173142)Study of Influence of Supplementing Qi and Activating Blood Circulation Herbs on Mitochondrial Energy Metabolism and Signal Transduction of Myocardial Ischemia Rats(No.81473552)The Basic Research Program(graduate program)of Beijing university of Chinese Medicine:Study of Influence of Supplementing Qi and Activating Blood Circulation Herbs on Notch Signal Network of Myocardial Infarction Rats(No.2016-JYB-XS034)
文摘OBJECTIVE: To investigate the effect of Yiqihuoxue prescription(YQHX) from Traditional Chinese Medicine(TCM) on myocardial glucose and lipid metabolism after myocardial infarction via the cross talk between the liver kinase B1(LKB1)-dependent Notch1 and adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK). YQHX was prepared with substances with properties that benefit, to activate blood circulation based on the TCM theory.METHODS: Animal models of myocardial infarction were established by ligating Sprague Dawley rats' left anterior descending coronary arteries. The animals were randomly divided into a myocardial infarction(MI) group, a YQHX group, a perindopril group, a γ-secretase inhibitor, Notch signal inhibitor(DAPT) group, a DAPT+YQHX group and a sham group. The related drugs were administered on the second day after operation, and changes in the relevant indexes were examined on weeks 1 and 4.Changes in cardiac structure and function were examined by echocardiography. The glucose and free fatty acids(FFA) were examined by ELISA. The expression of Notch, LKB1 and AMPK m RNA was examined by a real-time fluorescence quantitative method. The expression of glucose transporter 4(GLUT4), and the expression of total acetyl-Co A carboxylase(ACC) and its phosphorylation were examined by western blotting.RESULTS: Compared with the sham group, the expression of Notch, LKB1 and AMPK m RNA in the MI group was lower. Compared with the MI group, the expression of these m RNAs in the YQHX and perindopril groups was higher, and their expression in the DAPT group was lower. At all time points, the protein expression of GLUT4 and p ACC decreased in the MI group. On week 1, the expression of p ACC protein was higher. In the DAPT group, the expression of p ACC protein decreased. Compared with the YQHX group, the expression of p ACC protein in the DAPT + YQHX group was lower. On week 4,compared with the MI group, the expression of GLUT4 protein in the YQHX group and the perindo-pril group was higher. The expression of GLUT4 protein in the DAPT group decreased. Compared with the YQHX group, the expression of GLUT4 protein in the DAPT+YQHX group was lower. There was no significant difference in the expression of ACC protein between the groups.CONCLUSION: YQHX promoted cross talk between the LKB1-dependent Notch1 and AMPK in myocardial tissue after myocardial infarction. Furthermore,it regulated the glucose and lipid metabolism of cardiomyocytes at different time points, thereby ameliorating the cardiac energy metabolism via different mechanisms and protecting the heart.
基金Supported by Ministry of Education of the People's Republic of China:a Mechanism Study of Electro-Acupuncture EX-B3's Effect on Pancreas PDX-1 of Goto-Kakizaki Rats(No.313010)
文摘OBJECTIVE: To investigate the effect of low frequency electro-pulse acupuncture(EA) on blood glucose in rats with streptozotocin-induced type 2diabetes, and the possible mechanism underlying the action.METHODS: Rat models were established with high fat feeding and intraperitoneal injection of streptozotocin(STZ)(30 mg/kg). Rats with a random blood glucose > 16.7 mmol/L and blood glucose at 2 h-point of oral glucose tolerance test(OGTT) > 11.1 mmol/L were included as diabetic rats, and randomly divided into model group, EA Weiwanxiashu(EX-B 3) group, EA Zusanli(ST 36)group, glimepiride group, and EA non-acupoint group(n = 12). EA(2 Hz continuous wave, 2 m A,20 min/day, 6 days/week, 4 weeks) and intra-gastric administration of glimepiride were applied as interventions. With fasting blood glucose and OGTT tested at the end of the intervention, thestudy observed the patterns of hypoglycemic effects. For mechanism study, it observes hematoxylin and eosin staining and Masson staining of pancreas paraffin sections, protein expression of glucagon-like peptide 1 receptor(GLP-1R) in the pancreas and skeletal muscle, glucose transporter 4(GLUT4) protein expression in skeletal muscle membrane, to detect whether EA controls blood glucose via regulation of GLP-1R.RESULTS: EA Weiwanxiashu(EX-B 3) significantly increased model rats' pancreas GLP-1R, and GLUT4 of skeletal muscle membrane; the therapy significantly decreased model rats' skeletal muscle GLP-1R, restored pancreas morphology, and reduced fasting blood glucose and insulin resistance indices.CONCLUSION: EA Weiwanxiashu(EX-B 3) alone has significant effect on glycemia. EA Weiwanxiashu(EX-B 3) plus glimepiride further strengthen the effect. The regulation of the GLP-1R in pancreas and skeletal muscle might be mechanism underpinning the effect.
基金National Basic Research Program of China(973 Program,Grant No.2013CB932501)Beijing Natural Science Foundation(Grant No.7131009)National Natural Science Foundation of China(Grant No.81373343)
文摘Most of antieancer agents can not be used for treatment of brain glioma due to the existence of the blood brain barrier (BBB). The over-expression of glucose transporters (GLUTs) on the BBB and brain glioma cells enables the possibility that the GLUTs ligand modified drug carrier transports across the BBB, and targets to the brain glioma cells. The objectives of the present study were to synthesize a new glucose conjugate material, TPGS1000-Glu, develop a kind of TPGSI00o-Glu modified epirubicin liposomes, and evaluate their efficacy. The studies were performed on the BBB co-culture model and brain glioma cells in vitro. TPGS 1000-Glu was synthesized by conjugating TPGSlo00_COOH with 4-aminophenyl-[3-D-glucopyranoside (Glu), and confirmed by MALDI-TOF-MS spectrum. TPGS^0oo-GIu modified epirubicin liposomes were prepared with a high drug encapsulation efficiency (〉97%), a nanosize (approximately 90 nm), and a minimal drug leakage in fetal bovine serum (FBS)-containing buffer system. The BBB co-culture model was established, and after applying TPGSl0oo-Glu modified epirubicin liposomes to the model, transport of liposomal drug across the BBB was evidenced. Besides, TPGS1000-Glu modified epirubicin liposomes showed the strongest cellular drug uptake and anti-glioma efficacy after transport across the BBB in vitro. The synthesized TPGS1000-Glu material could offer a new targeting ligand for the BBB, while the developed TPGS1000-Glu modified epirubicin liposomes might provide a potential anticancer formulation for treatment of brain glioma.
基金Beijing Excellent Talents Training Assistance(Grant No.2017000082595G244)the Health and Research Bureau of Tongzhou District(Grant No.TWKY-2016-QN-01-58)。
文摘Canagliflozin(CANA)is a sodium-glucose co-transporter 2 inhibitor.One of the important mechanisms of CANA is the inhibitory effect on the glucose uptake in the proximal tubule of the nephron,and the other mechanism can be the reduction of inflammatory cytokine expression monocytes and macrophages.It is proved by FDA for the management of type 2 diabetes.In the present work,we summarized the publication and clinical evidence of the CANA on healthy individuals and those with related metabolic diseases,such as type 1 and 2 diabetes,obesity,or cardiovascular and kidney diseases.This drug has been reported to offer potential advantages in regulating body weight and reducing heart failure,hypoglycemia,and stroke risk in patients with type 2 diabetes.Some in vitro and animal experiments also show that this drug has good effects on cancer treatment.However,some case reports and experiments also show the side effect of CANA,such as amputation,fracture,and pancreatitis,while the mechanism is still unknown.Overall,CANA has a good effect on the management of type 2 diabetes by reducing the risk of kidney failure,cardiovascular diseases,and stroke.However,as a new drug,more clinical trials and experiments of CANA should be carried out in the future.
基金ThisstudywassupportedbytheNationalNaturalScienceFoundationofChina (No 39870 2 88)
文摘Objective To evaluate the role of glucose transporter 1 (GLUT1) in the glucose uptake of glomerular mesangial cells.Methods Cultured human glomerular mesangial cells were used. The expressions of glucose transporter 1 mRNA and protein were detected with reverse transcription-polymerase chain reaction (RT-PCR), flow cytometry and immunofluorescence staining. Glucose uptake was determined with 2-deoxy-[3H]-D-glucose uptake assay.Results The expressions of GLUT1 mRNA and proteins were detected in human mesangial cells. Glucose uptake and its kinetics assay showed that GLUT1 is a functional glucose transporter in cultured human mesangial cells, and that its function could be inhibited by the specific inhibitor, Phloretin. Conclusion GLUT1 is the predominant glucose transporter in human mesangial cells, which has the kinetic characteristics of high affinity and low capacity for D-glucose. This suggests that in order for mesangial cells to take up excessive quantities of glucose, as in diabetes, changes in glucose transporter expression, translocation or activity may be required.