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OBJECTIVE To investigate the effects of Angelica sinensis polysaccharide on the apoptosis of cardiomyocytes in diabetic KK-Ay mice. METHODS KK-Ay mice were randomly divided into model group， metformin group （200 mg/kg） and A. sinensis polysaccharide high-dose， medium-dose and low-dose groups （400， 200 and 100 mg/kg）； C57BL/6J mice were included in blank group， with 8 mice in each group. Each group was given relevant medicine intragastrically or normal saline， once a day， for consecutive 4 weeks. After the final administration， the levels of fasting glucose， total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C） and insulin （INS） were detected； the protein expressions of B-cell lymphoma 2 （Bcl-2）， cleaved- caspase-3， apoptosis signal-regulated kinase 1 （ASK1）， phosphorylated c-Jun N-terminal kinase （p-JNK）， phosphorylated inositol- requiring enzyme 1α （p-IRE1α） in myocardium， and apoptosis in cardiomyocytes were also detected. RESULTS Compared with model group， the fasting glucose， TC and LDL-C content， apoptotic rate of cardiomyocyte， protein expressions of p-JNK and p- IRE1α， ASK1， cleaved-caspase-3 were significantly lower in the metformin group and A. sinensis polysaccharide medium-dose， high-dose groups； INS level and relative expression of Bcl-2 protein were significantly increased （P＜0.05 or P＜0.01）. CONCLUSIONS A. sinensis polysaccharide can improve the levels of blood glucose and blood lipid and inhibit cardiomyocyte apoptosis in diabetic KK-Ay mice， and the mechanism may be related to the inhibition of IRE1/ASK1/JNK signaling pathway.
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Aim To evaluate the effect of E-se extract on insulin resistance in KK-Ay mice with spontaneous type 2 diabetes anrl explore its mechanism.Methods Ten C57/6J mice were assigned to a normal control group.Fifty KK-Ay model mice were randomly divided into model group, positive control group ( rosiglita- zone, 2.67 mg • kg 1 ), and low- ( 0.75 g • kg 1 ) , medium- ( 1.50 g • kg 1 ) , and high-dose ( 3.00 g • kg ') E-se groups, with 10 mice in each group.All mice were measured for body weight and fasting blood glucose weekly, insulin tolerance on the 32nd day, and insulin after the last administration on the 35th day, and the insulin resistance/sensitivity indexes were calculated.The pancreas was stained by hematoxylin- eosin ( HE ).Islet cell apoptosis was detected by TUNEL staining.Glucagon-like peptide-1 ( GLP-1 ) was detected by immunohistochemistry.Results j j Compared with the model group, the E-se groups showed reduced body weight, fasting blood glucose, serum insulin concentration, and insulin resistance in¬dex, elevated insulin sensitivity index, decreased le¬sion grading score of pancreatic tissues and apoptosis percentage of islet cells, and increased content of GLP- 1 protein in pancreatic tissues.Conclusions E-se ex¬tract can improve insulin resistance by reducing serum insulin level, inhibiting islet cell apoptosis, and in¬creasing the sensitivity of the body to insulin.
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Este artigo aborda como o intelecto interage com as experiências emocionais. Constata-se existir cada vez mais indivíduos, de diferentes faixas etárias, que priorizam a busca de informações instantâneas sem investir no desenvolvimento do pensar/conhecer, bem como indivíduos que se desenvolvem intelectualmente, porém não conseguem lidar de modo compatível com as experiências emocionais. Propomos, no presente trabalho, uma reflexão sobre os aspectos defensivos que permeiam o desenvolvimento emocional/intelectual segundo Bion e Winnicott.
This article discusses how the intellect interacts with emotional experiences. Evidence shows that there are more and more individuals from different age groups who prioritize the search for instant information without investing in the development of thinking / knowing, as well as individuals who develop intellectually, but cannot cope with the emotional experiences. In this paper, we propose a reflection on the defensive aspects that permeate the emotional / intellectual development according to Bion and Winnicott.
Este artículo analiza cómo el intelecto interactúa con las experiencias emocionales. Existen evidencias de que hay cada vez más personas de diferentes grupos de edad que priorizan la búsqueda de informaciones instantáneas sin invertir en el desarrollo del pensamiento / conocimiento, así como personas que se desarrollan intelectualmente, pero no pueden hacer frente a las experiencias emocionales. En este artículo, proponemos una reflexión sobre los aspectos defensivos que impregnan el desarrollo emocional / intelectual según Bion y Winnicott.
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Aim To study the anti-diabetic effects of natural product gastrodin ( GSTD ) in KK-Ay mice. Methods C57BL/6J mice were used as normal con-trol, while KK-Ay diabetic mice were divided into five groups, namely the untreated group, GSTD 10 mg· kg-1, 20 mg·kg-1, 50 mg·kg-1 groups, and the metformin ( Met) 200 mg·kg-1 group, respectively, with 10 mice in each group. GSTD and Met were ad-ministered intragastrically for eight weeks. Before ex-periment and once a week during the experiment, the fasting blood glucose ( FBG) levels were determined. During the 7th week of drug treatment, oral glucose tolerance test ( OGTT ) and insulin tolerance test ( ITT) were conducted. Before the end of experiment, 24 h urine samples were collected for the assay of rela-tive parameters. At the end of experiment, blood sam-ples were collected for the assay of glycosylated hemo-globin ( GHb) ; serums were isolated for the determina-tion of insulin concentration and other biochemical in-dexes. After sacrifice, the livers, kidneys, and pan-creases of the mice were harvested for pathological ex-amination; the contents of advanced glycation end product ( AGE) and triglyceride ( TG) in renal tissues were assayed by kits. Results GSTD at all doses sig-nificantly reduced FBG, urine glucose, GHb, serum insulin level, and the insulin resistance index in KK-Ay diabetic mice. In addition, GSTD greatly inhibited body weight gain and improved glucose tolerance and insulin tolerance ( P <0.05 or P <0.01 vs untreated group ) . The pathological examination showed that GSTD significantly increased the glycogen content of liver tissues, reduced islet volume and improved its pathological changes. In addition, the glomerulosclero-sis induced by diabetes was greatly ameliorated by GSTD. Meanwhile, GSTD greatly reduced serum crea-tine ( Scr) , 24 h urine amount, 24 h urine total pro-tein and microalbumin ( mAlb) , as well as renal AGE and TG contents in KK-Ay mice ( P <0.05 or P <0.01 vs untreated group) . The anti-diabetic effect of GSTD at 50 mg·kg-1 was comparable to that of 200 mg·kg-1 of Met. Conclusions When used to treat KK-Ay diabetic mice, GSTD has potent activities in lowering blood glucose, improving insulin resistance and ameliorating diabetic nephropathy. However, the detailed mechanisms of GSTD in modulating glucose metabolism and increasing insulin sensitivity still need further investigation.
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Objective: To explore the effect of Gegen Qinlian Decoction (GGQLD) on LPS, TNF-α, IL-6, and intestinal flora in diabetic KK-Ay mice. Methods: C57BL/6J mice with ordinary feed were taken as the normal control group and orally administrated with equal distilled water. The KK-Ay mice fed with high-fat diet were divided into five groups: pioglitazone group, blank group (model group), high, medium, and low dose GGQLD group, and orally administrated with pioglitazone hydrochloride (5 mg/kg), distilled water, and GGQLD (crude drug 40, 13.3, and 4.44 g/kg), respectively. The oral administration for six groups lasted for four weeks. Tumor necrosis factor (TNF-α), interleukin 6 (IL-6), and endotoxin (LPS) levels in the plasma were determined by enzyme-linked immunosorbent assay (ELISA); Gut microbial communities were assayed by polymerase chain reaction (PCR) and PCR-denaturing gradient gel electrophoresis (PCR-DGGE) methods. Results: Compared with the model group, the LPS levels in the plasma of mice were significantly reduced by 15.61% and 14.48% respectively in the Gegenqinlian Decoction of high and medium dose group (P < 0.05), the IL-6 levels in plasma of mice were significantly reduced by 56.86%, 37.12% and 30.21% respectively in high, medium, and low dose GGQLD group (P < 0.05), and the TNF-α levels in plasma of mice were significantly reduced by 28.32%, 30.70%, and 23.42% respectively in high, medium, and low dose GGQLD group (P < 0.05). The number of DGGE bands in high dose group significantly increased, and by cloning, sequencing, and Blast analysis, Lactobacillus johnsonii only existed in the high dose group; The results showed that GGQLD could regulate the structure of intestinal flora in KK-Ay mice. Conclusion: The mechanisms of anti-diabetic effects of GGQLD in type 2 diabetic KK-Ay mice are probably related with the anti-inflammation and regulation of intestinal flora.
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Objective:To explore the improvement effect of rhein lysinate (RHL)on the insulin resistance in the KK/HlJ diabetes mellitus (DM ) mice induced by streptozotocin (STZ ), and to elucidate its mechanism. Methods:The KK/HlJ diabetic mouse models were made by intraperitoneal injection of STZ (50 mg· kg-1 )and fed with DM diet.A total of 48 mice were divided into normal control group,model group,low dose of RHL group (25 mg·kg-1 )and high dose of RHL group (50 mg·kg-1 ) (n= 12).All the mice were treated for 16 weeks. The levels of fasting glucose (FBG),total cholesterol (TC)and triglyceride (TG)of the mice were measured by glucose oxidase method.HE staining was used to observe the morphology of pancreas tissue of the mice.The insulin level in pancreas islet tissue was detected by immunohistochemistry method.The levels of insulin and of C reactive protein (CRP)in serum and tumor necrosis factorα(TNF-α)and interleukin 6 (IL-6)in liver tissue of the mice were detected by enzyme linked immunosorbent assay (ELISA)method.The expression levels of glycogen synthesis related genes (PI3K,AKT and GSK-3β)phosphorylation were detected by Western blotting method. Results:Compared with model group,the levels of FBG,TG and TC of the mice in low and high doses of RHL groups were significantly decreased (P < 0.05),but there was no significant difference in the insulin level (P >0.05).Compared with model group,the levels of CRP in serum and the levels of TNF-αand IL-6 in liver tissue of the mice in low and high doses of RHL groups were significantly decreased (P <0.01).The HE staining results showed that compared with model group,the islet morphology of the mice in low and high doses of RHL groups was partially restored,and the occasional inflammatory infiltration was observed.The immunohistochemical staining results showed that compared with model group,the brown granular substance in the islets of the mice in low dose of RHL group was significantly reduced,which was disappeared in high dose of RHL group.Compared with model group,the expression levels of glycogen synthesis related genes (PI3K,AKT and GST-3β)phosphorylation of the mice in low and high doses of RHL groups were increased (P <0.01).Conclusion:RHL has improvement effect on the insulin resistance in the KK/HlJ DM mice induced by STZ,and the mechanism may be related to promoting the glycogen synthesis.
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Objective To study the effect and mechanism of Water extract from Jiangtang Decoction (WEJTD) on diabetes mellitus and diabetic nephropathy (DN) in spontaneous type 2 diabetes mellitus model KK-Ay 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 put into metabolism cages,and the food-intake,water-intake and urine volume were calculated and collected.Blood were collected to detect the concentration of IL-6,ICAM-1 and TNF-α.Then mice were executed,and HE staining and PASM staining were used to check the effect of WEJTD on kidney.Western blotting and qRT-PCR were used to detect the concentration of PI3K,Akt,NF-κB,IL-6,ICAM-1 and TNF-α in kidney.Results WEJTD can alleviate the symptoms of diabetes,such as food ration,polydipsia and polyuria (P ＜ 0.05,0.01,and 0.001);Relief the pathological changes of kidney and significantly decreased glycogen deposition (P ＜ 0.001),down-regulate the increase of IL-6,ICAM-1 and TNF-α in serum and kidney (P ＜ 0.05,0.01 and 0.001),up-regulate the phosphorylation of PI3K and Akt (P ＜ 0.05,0.01,and 0.001),and inhibit the phosphorylation of NF-κB (P ＜ 0.001).Conclusion WEJTD had positive effects on kidney morphology of KK-Ay,and the underlying mechanism might be related to the regulation of PI3K-Akt and NF-κB-mediated inflammation.
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Aim To investigate the effects of Tongxin-luo capsule on oxidative stress in diabetic peripheral neuropathy (DPN )mice and its mechanisms.Meth-ods KK/Upj-Ay mice were divided into model, Tongxinluo low-dose group, Tongxinluo middle-dose group and Tongxinluo high-dose group.C57BL/6 mice were selected as control group.Mice were given drugs intragastrically for 12 weeks.Paw withdrawal latency, motor nerve conduction velocity (MNCV)were detec-ted.Activity of superoxide dismutase (SOD),gluta-thione peroxidase (GSH-Px)and content of malondial-dehyde (MDA)in blood were detected by colorimetric method.The expression of heme oxygenase-1 (HO-1 ),γ-glutamyl cysteine synthetase (γ-GCS ) of sciatic nerve was examined by real time PCR and Western blot.The protein expression of p38 MAPK,p-p38 MAPK,JNK,p-JNK,ERK,p-ERK was examined by Western blot.Results Compared with model group, paw withdrawal latency was increased and MNCV was faster in Tongxinluo group (P <0.05 ,P <0.0 1 ). SOD and GSH-Px contents significantly increased, MDA content decreased (P <0.01 ).HO-1,γ-GCS mRNA and protein expression significantly increased (P<0.05,P <0.01 )in Tongxinluo group.p-p38 MAPK protein expression decreased in Tongxinluo group (P<0.05 ).Conclusion Tongxinluo can in-hibit oxidative stress in DPN of mice via suppressing the phosphorylation of p38 MAPK.
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OBJECTIVE: To observe the glucose tolerance and evaluate the hypoglycemic effect of MBX-2982 respectively in the normal mice and in the KK-Ay mice. And further pharmacokinetics investigation was experimented in rats. METHODS: The influence of glucose tolerance was evaluated in KM mice which underwent a single dose of MBX-2982. Body weight, fasting blood glucose, glucose tolerance, triglyceride, serum insulin were all tested in order to evaluate the hypoglycemic effect on KK-Ay mice. The pharmacokinetics of MBX-2982 suspension and solution were investigated in rats to calculate the oral bioavailability. RESULTS: The blood glucose of each test point were all reduced after MBX-2982 (3, 10, 30 mg · kg-1) were administered orally to KM mice. After MBX-2982 (10, 30 mg · kg-1) treatment to KK-Ay mice for 4 weeks, the fasting blood glucose and triglyceride were significantly reduced and the serum insulin was remarkably increased. Meanwhile the area under glucose curve was significant reduced of 30 mg · kg-1. After oral administration of MBX-2982 (4 mg · kg-1) in rats, the oral bioavailability of suspension (0.4% CMC) and solution (DMSO-Cremopor EL-NS = 1:1:8) were 35.2% and 98.2% receptively. CONCLUSION: Animal experiment results show that the MBX-2982 as a GPR119 agonists had a good hypoglycemic effect. The absolute bioavailability of the solution is closed to 100%, which is higher than that of suspension.
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This article was aimed to study the effect ofQiwei granules on the podocyte in KK-Ay mice kidney. The 28 8-week-old male KK-Ay mice were randomly divided into the model group, low-dosage, middle-dosage and high-dosageQiwei granule group. Eight C57BL/6J mice were used as the normal control. The general conditions, blood glucose and 24 h albuminuria were recorded in the experiment. After 10-week treatment, renal indexes including serum creatinine and urea nitrogen were measured. The kidneys of mice were collected and measured. The hematoxylin and eosin (HE), Masson’s Trichrome, and periodic acid-Schiff (PAS) were used on renal tissues of mice. The immunohistochemical staining for WT-1 was made. Software analysis was combined in the calculation of renal podocyte amount. Western blot was used in the detection of nephrin protein expressions in the kidney of mice. RT-PCR was used in the detection of nephrin mRNA expression. The results showed that compared with the model group, the body weight, blood glucose, 24 h albuminuria and the serum creatinine were obviously decreased after 10-week treatment ofQiwei granules. It can effectively improve the glomerular mesangial proliferation and preserve the podocyte number. Meanwhile, after the treatment ofQiwei granules, the nephrin protein expression and mRNA expression were obviously higher than the model group. It was concluded thatQiwei granules probably managed nephrin expression to improve the podocyte injury in the diabetic nephropathy of KK-Ay mice.
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Aim To find the material foundation of treatment for diabetes in Coptidis Rhizoma ( RC ) . Methods The antihyperglycemic effect of RC alka-loids ( berberine, coptisine, palmatine, epiberberine, and jatrorrhizine) was evaluated in spontaneity diabe-tes KK-Ay mice. Results After 40 days′ oral admin-istration ( 225 mg · kg-1 · d-1 , ig ) , berberine and coptisine significantly suppressed the elevated fasting blood glucose level and ameliorated the glucose toler-ance . Body weight gain of KK-Ay mice was significant-ly decreased in the epiberberine-treated group. Berber-ine improved insulin resistance and jatrorrhizine in-creased the SOD activity, decreased the MDA level. Conclusions These results indicate that the main an-tihypoglycemic effect constituents are berberine and coptisine, while they show different mechanisms. Pal-matine, epiberberine and jatrorrhizine display different potential roles in the treatment of diabetes. The meth-ylene-dioxy groups at the C-2 , C-3 , C-9 and C-10 po-sitions are indispensable for antihyperglycemic effect of RC alkaloids.
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OBJECTIVE: To study the effects tetrahydrocurcumin-solid dispersion on KK-AY mice. METHODS: C 57/6 J mice were used as controls, KK-Ay mice were randomly divided into model group, tetrahydrocurcumin-solid dispersion groups(100, 50, 15 mg · kg-1) and rosiglitazone group(2.67 mg · kg-1), gavage for 35 d, mouse weight, fasting blood glucose, oral glucose tolerance, serum insulin and blood lipid indexes were detected. RESULTS: The weight mice tetrahydrocurcumin-solid dispersion group (100 mg · kg-1) on twenty-first days administration began to decrease, and maintained at a low level during the administration; tetrahydrocurcumin-solid dispersion in each dose group showed impaired fasting blood glucose lowering from the fourteenth day after the administration began, and maintained at a low level during the administration, tetrahydrocurcumin-solid dispersion in each dose group can decrease postprandial blood glucose and AUC value; tetrahydrocurcumin-solid dispersion in each dose group can decrease the value TC, LDL-C, increase the insulin sensitivity index, tetrahydrocurcumin-solid dispersion in each dose group glycosylated serum protein values were decreased, while only in the 100 mg · kg-1 group was statistical significant differences compared with the model group. CONCLUSION: Tetrahydrocurcumin-solid dispersion, which can effectively reduce the blood glucose levels KK-AY mice, and has good effect on glucose metabolism, lipid metabolism. The mechanism action may be related to the increase insulin sensitivity.
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Objective To measure the organ weights , blood physiological and biochemical parameters of KK /Upj-Ay/J.Methods KK/Upj-Ay/J mice at five and ten weeks of age were selected , and the organ weights , blood physiological and biochemical parameters were observed .Results Parts of the organ weights , blood physiological and biochemical parameters of different ages and sexes were significant differences .The fasted blood glucose of KK/Upj-Ay/J mice reached 7.0mmol/L at 10 weeks of age .Conclusion The results show that the organ weights , blood physiological and biochemical parameters are affected by age and gender of KK /Upj-Ay/J mice.The fasted blood glucose reached the diabetes level at 10 weeks of age .
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Objective To identify the candidate genes in the vicinity of a susceptibility locus (urinary albumin 1,UA-1) contributing to the development of albuminuria in type 2 diabetic KK/Ta mice. Methods Total RNA was extracted from the kidneys of KK/Ta (n=3) and BALB/c (n=2) mice at 20 weeks of age.The gene expression profile in kidney was investigated using the Affymetrix Murine Genome U74Av2 array.Competitive RT-PCR was used to confirm the differential expression of syndecan-4 which located in the vicinity of UA-1.Genome DNA was extracted from KK/Ta and BALB/c mice.DNA sequence analysis of the coding and promotor region of syndecan-4 gene was conducted. Results In the vicinity of the susceptibility locus (UA-1)contributing to the development of albuminuria in type 2 diabetic KK/Ta mice,10 candidate genes that showed differential expression were identified.Among them,the gene expression of syndecan-4in KK/Ta kidneys at 20 weeks of age was up-regulated by 26.1 times of age-matched BALB/c kidneys.Sequence analysis revealed two synonymous polymorphisms in the coding region (A93C and T216C) and three polymorphisms in the promoter region (-T263C,-T396C and -G669A) of the syndecan-4 gene.The TATA box was found at 321 bp upstream from the transcription start site,and the T263C polymorphism was located in the binding site of transcription factor Clox.Conclusions Syndecan-4 gene is mapped in the vicinity of the susceptibility locus contributing to the development of albuminuria in type 2 diabetes.The gene expression of syndecan-4 in KK/Ta kidneys is up-regulated than that in age-matched BALB/c kidneys at 20 weeks of age.Thus syndecan-4 may be one of the potential candidate genes responsible for diabetic nephropathy.Sequence differences in the promoter region influence the expression levels of syndecan-4 genes in KK/Ta kidneys.
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We studied the effect of Chinese tea on obese mice (KK-<i>A</i><sup>y</sup>) as a preliminary stage in a study to investigate the effect of Kampo formulations on body weight. Thirty male KK-<i>A</i><sup>y</sup> mice aged six weeks were given basic food ad libitum combined with oolong and tuo tea or with jasmine tea for 16 weeks. Body weight was measured regularly during this period. On completion of the study, the mice were examined biochemically, and various organs were investigated histologically.<br>The control mice were given tap water ad libitum. Two groups given tea showed lower body weight than the controls throughout the study. Those given jasmine tea, in particular, recorded the maximum rate of weight decrease, i. e. 16.5%, at 5 weeks, even though the mean food consumption was high in this group during the study.<br>Many factors are involved in body weight, and we could not elucidate the mechanism of weight loss. The study, however, demonstrated that jasmine tea is effective in decreasing the weight of mature KK-<i>A</i><sup>y</sup> obese mice.
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KK-Ay mice with type 2 diabetes were divided into metformin plus high-fat diet,metformin plus low-fat diet,high fat diet alone and low fat diet alone groups.AMP-activated protein kinase(AMPK)activity was measured in skeletal muscle.The results showed that metformin and low-fat diet were able to increase AMPK activity.However,no additive effect on AMPK activity by metformin and low-fat diet was found.