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Isoliquiritigenin (ISL) is an active chalcone compound isolated from licorice. It possesses anti-inflammatory and anti-oxidative activities. In our previous study, we uncovered a great potential of ISL in treatment of type 2 diabetes mellitus (T2DM). Therefore, this study aims to reveal the mechanism underlying the alleviatory effects of ISL on T2DM-induced glycolipid metabolism disorder. High-fat-high-sugar diet (HFD) combined with intraperitoneal injection of streptozotocin (STZ) were used to establish T2DM mice model. All animal experiments were carried out with approval of the Committee of Ethics at Beijing University of Chinese Medicine. HepG2 cells were used in in vitro experiments, and sodium palmitate (SP) was applied to establish insulin resistance (IR) model cells. The effects of ISL on body weight, fasting blood glucose levels, and pathological changes in the livers of mice were examined. Enzyme-linked immune sorbent assay (ELISA) and real-time quantitative PCR (RT-qPCR) were applied to detect the regulatory effects of ISL on key targets involved in glucolipid metabolism. Additionally, molecular docking and analytical dynamics simulation methods were used to analyze the interaction between ISL and key target protein. The results indicate that ISL significantly downregulates the transcriptional levels and inhibits the activities of key enzymes involved in gluconeogenesis, including pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK), and fructose-1, 6-bisphosphatase (FBP). It also downregulates the transcriptional and protein levels of hepatocyte nuclear factor 4α (HNF4α) and cAMP response element binding protein (CREB), the two transcriptional factors involved in gluconeogenesis. Thus, ISL inhibits hepatic gluconeogenesis in T2DM mice. In addition, ISL reduces total cholesterol (TC) and triglyceride (TG) levels in the livers of T2DM mice. Moreover, ISL downregulates the mRNA levels of lipogenesis genes and upregulates those of genes involved in fatty acid oxidation, lipid uptake, and lipid export. In conclusion, ISL suppresses hepatic gluconeogenesis, promotes lipolysis, and restrains lipogenesis in T2DM mice, thereby improving the abnormal glycolipid metabolism caused by T2DM.
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Objective:To explore the changes and significance of triglyceride-glucose (TyG) index, C-peptide and lipid metabolism in patients with type 2 diabetes mellitus (T2DM) complicated with hyperuricemia (HUA).Methods:A prospective research method was adopted. One hundred and three patients with T2DM treated in Tongling Hospital of Traditional Chinese Medicine were selected between March 2019 and November 2021, and they were divided into HUA group (34 cases) and non-hyperuricemia (NUA) group (69 cases) according to whether they were complicated with HUA. The general data, fasting blood glucose (FBG), serum uric acid (SUA), serum C-peptide, total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and serum creatinine (SCr) were compared among the patients, and the TyG index was calculated. The relationship between the above different indicators and SUA was analyzed, and the possible risk factors of HUA with T2DM were analyzed.Results:There were no statistical differences in gender, disease course of diabetes and smoking history between HUA group and NUA group ( P>0.05), but the age in HUA group was younger than that in NUA group: (46.71 ± 10.23) years old vs. (58.74 ± 11.22) years old, and the body mass index (BMI) was higher than that in NUA group: (24.48 ± 2.26) kg/m 2 vs. (22.05 ± 2.14) kg/m 2, and the proportion of patients with alcohol drinking history was higher than that in NUA group: 55.88% (18/34) vs. 24.64% (17/69) ( P<0.05). There were no statistically significant differences in the levels of FBG, TC and LDL-C between HUA group and NUA group ( P>0.05), but the TG, TyG index, C-peptide, SUA and SCr were higher in HUA group than those in NUA group: (2.68 ± 0.57) mmol/L vs. (1.57 ± 0.33) mmol/L, 10.58 ± 3.52 vs. 7.03 ± 2.14, (2.59 ± 0.67) μg/L vs. (2.07 ± 0.41) μg/L, (356.74 ± 56.47) μmol/L vs. (319.87 ± 50.92) μmol/L, (72.05 ± 8.31) μmol/L vs. (58.59 ± 8.04) μmol/L, while the HDL-C level was lower than that in NUA group: (1.09 ± 0.33) mmol/L vs. (1.38 ± 0.41) mmol/L ( P<0.05). Pearson correlation results showed that TyG index, C-peptide, TG, LDL-C and SCr were positively correlated with SUA ( r = 0.42, 0.49, 0.41, 0.30 and 0.51; P<0.05), and HDL-C was negatively correlated with SUA ( r = -0.47, P<0.05). Multivariate Logistic regression analysis showed that increased BMI, alcohol drinking, increased TyG index and C-peptide, TG and SCr and reduced HDL-C were risk factors for HUA in patients with T2DM ( P<0.05). Conclusions:The TyG index, serum C-peptide and TG in patients with T2DM complicated with HUA are abnormally increased and are positively correlated with SUA, while HDL-C is decreased and is negatively correlated with SUA. High BMI, alcohol drinking, high TyG index, C-peptide, TG and SCr, and low HDL-C level are risk factors for HUA in patients with T2DM.
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The obstruction of post-insulin receptor signaling is the main mechanism of insulin-resistant diabetes. Progestin and adipoQ receptor 3 (PAQR3), a key regulator of inflammation and metabolism, can negatively regulate the PI3K/AKT signaling pathway. Here, we report that gentiopicroside (GPS), the main bioactive secoiridoid glycoside of Gentiana manshurica Kitagawa, decreased lipid synthesis and increased glucose utilization in palmitic acid (PA) treated HepG2 cells. Additionally, GPS improved glycolipid metabolism in streptozotocin (STZ) treated high-fat diet (HFD)-induced diabetic mice. Our findings revealed that GPS promoted the activation of the PI3K/AKT axis by facilitating DNA-binding protein 2 (DDB2)-mediated PAQR3 ubiquitinated degradation. Moreover, results of surface plasmon resonance (SPR), microscale thermophoresis (MST) and thermal shift assay (TSA) indicated that GPS directly binds to PAQR3. Results of molecular docking and cellular thermal shift assay (CETSA) revealed that GPS directly bound to the amino acids of the PAQR3 NH2-terminus including Leu40, Asp42, Glu69, Tyr125 and Ser129, and spatially inhibited the interaction between PAQR3 and the PI3K catalytic subunit (P110α) to restore the PI3K/AKT signaling pathway. In summary, our study identified GPS, which inhibits PAQR3 expression and directly targets PAQR3 to restore insulin signaling pathway, as a potential drug candidate for the treatment of diabetes.
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OBJECTIVE：To st udy the improvement effects and its mechan ism of alisol B 23-acetate on glycolipid metabolism disorder in obesity model mice. METHODS ：The mice was given high-fat diet for 10 weeks to induce obesity model. Model mice were randomly divided into model group ，orlistat group （positive control ，15.6 mg/kg）， alisol B 23-acetate low-dose ， medium-dose and high-dose groups （7.5，15，30 mg/kg），with 10 mice in each group. Another 10 mice fed with normal diet were set as normal group. The mice in normal group and model group were given water intragastrically ，and administration groups were given the corresponding drugs intragastrically ，with the volume of 20 mL/kg，once a day ，for consecutive 4 weeks. After last medication，body weight ，waist circumference ，body fat ，muscle and body fluid mass were measured ；the serum levels of blood lipids indicators （TC，TG，HDL-C，LDL-C）and blood glucose were determined. The levels of PPAR-γ，NF-κB and IL-6 in liver tissue as well as serum level of TNF-α were determined by ELISA. The pathomorphological changes of visceral fat and liver tissue in mice were observed by HE staining. RESULTS ：Compared with normal group ，body weight ，waist circumference ，body fat and body fluid mass were significantly increased in model group （P＜0.01）；serum levels of TC ，TG，HDL-C，blood glucose and TNF-α，the levels of PPAR-γ，NF-κB and IL-6 in liver tissue were increased significantly （P＜0.05 or P＜0.01）；the structure of adipocytes was ruptured ，the volume of adipocytes was increased ，accompanied by inflammatory cell infiltration ；a large number of liver cells were edema ，and cytoplasm was loose and light stained，accompanied by fatty degeneration. Compared with model group ，the body weight ，body fat and body fluid mass as well as serum le vels of TG and TNF-α in alisol B 23-acetate groups were significantly reduced （P＜0.01）；the levels of TC and blood glucose in serum ，IL-6 in liver tissue were significantly decreased in alisol B 23-acetate medium-dose and high-dose groups （P＜0.05 or P＜0.01），and the level of PPAR-γ in liver tissue was increased significantly（P＜0.05 or P＜0.01）； the waist circumference and NF-κB levels in liver tissue in alisol B 23-acetate high-dose group were decreased significantly （P＜ 0.01）；serum level of HDL-C in alisol B 23-acetate medium-dose group were decreased significantly （P＜0.01）；the adipocytes were closely arranged and small in size ；the hepatocytes were mild to moderate swelling ，a small amount of cytoplasm was loose ， light stained or vacuolated ，and a small number of hepatocytes were accompanied by steatosis and small focal infiltration of inflammatory cells. CONCLUSIONS ：Alisol B 23-acetate can improve the disorder of glucose and lipid metabolism in obesity model mice ，and its mechanism may be related to the regulation of PPAR-γ，NF-κB，IL-6 levels in liver tissue and TNF-α levels in serum.
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Studies have shown that women's menopause caused by permanent cessation of ovarian function is closely related to lipid metabolism disorders. Er-xian Decoction has been used in the clinical treatment for gynecological diseases and has a good effect on diseases related to reduced sex hormone function. In this study, metabolomics was performed on bilateral ovariectomized model rats within 12 weeks after modeling to mimic the physiological state of menopausal women in different menopausal stages and Er-xian Decoction dosed model rats. The results of liver oil red O staining sections showed lipid metabolic disorder of bilateral ovariectomized model rats and the regulating effects of Er-xian Decoction. 46 potential biomarkers (6 steroid hormones, 3 sphingolipids, 11 phospholipids and 26 glycerides) in plasma and 32 potential biomarkers (1 steroid hormones, 20 phospholipids and 11 glycerides) in liver were obtained based on lipidomics analysis. Then, we analyzed the differential metabolic pathways and construct the lipid metabolism network significantly regulated by Er-xian Decoction. The results provided valuable information for in-depth understanding of the gradual changes on lipid metabolism disorders under menopausal conditions and the characteristics and mechanisms of compound Er-xian Decoction's regulatory effects. The study complied with the procedures established by the Animal Experiment Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and passed the animal experiment ethics examine (No. 00000918).
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Objective: To analyze the molecular biological mechanism of Shenqi Jiangtang Granules (SJG) in the treatment of lipid metabolism disorder based on network pharmacology and glucolipid metabolic disorders (GLMD) theory. Methods: The targets of SJG's active components for treatment of lipid metabolism disorder were screened and predicted by utilizing PubChem Search, Genecards database and Swiss target prediction online tool. The protein-protein interaction (PPI) network was established by using STRING database. Cytoscape 3.3.0 software was adopted to construct a disease-active component-potential target network. Gene ontology (GO) biological process and Kyoto Encyclopedia of Genes and Gnomes (KEGG) pathway enrichment analysis were performed using Clue GO. Results: A total of 115 active components of SJG and 22 targets related to lipid metabolism disorder were screened. The active components of SJG regulated intermediate-density lipoprotein particle remodeling, glycolytic process by regulation of transcription from RNA polymerase II promoter and leukotriene production involved in inflammatory response, and participated in AGE-RAGE signaling pathway, NF-κB signaling pathway, TNF signaling pathway and bile secretion. Conclusion: This study reflects the characteristics of multi-components, multi-targets, and multi-pathways of SJG, and provides new ideas and clues for new application of SJG, which is consistent with the GLMD theory.
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OBJECTIVE：To s tudy improvement effect and mech anism of ilicifoliosids alkaloid A （HBOA）on non-alcoholic fatty liver disease in rats. METHODS ：SD rats were randomly divided into blank control group ，model group ，Silybin capsule group（positive control ，26.25 mg/kg），HBOA high-dose ，medium-dose and low-dose groups （100，50，25 mg/kg），with 10 rats in each group. Except that blank control group fed normal feed ，the other groups were continuously fed with high-fat diet for 8 weeks to induce non-alcoholic fatty liver disease model. Form the 9th week ，blank control group and model group were given constant volume of 0.6％ CMC-Na solution ，and administration groups were given corresponding drugs by intragastric admini- stration，once a day ，for consecutive 4 weeks. The general information of rats were observed and the body weight increase ，organ （liver，kidney and spleen ）indexes were calculated ；the contents of AST ，ALT，TC，TG and NEFA in liver tissue were detected ， and SOD，GSH-Px activities and MDA content in the serum were also determined. The protein expression of PPARα in liver tissue was detected by immunohistochemistry. RESULTS ：Compared with blank control group ，the body mass increase and liver index of rats in model group were increased significantly （P＜0.01）；fat deposition could be observed in the liver ；the activities of SOD and GSH-Px in serum were reduced significantly ，and the contents of MDA ，the contents of AST ，ALT，TC，TG and NEFA in liver tissue were significantly increased ，and the protein expression of PPARα was decreased significantly（P＜0.01）. Compared with model group ，the body mass increase and liver index of the rats were decreased significantly in administration groups （P＜0.05 or P＜0.01），liver fat deposition was improved ，the activity of SOD and GSH-Px in serum （except for HBOA low-dose group ）were increased significantly while MDA content ，the contents of AST ，ALT，TC（except for HBOA low-dose group ），TG（except for HBOA low-dose group ） and NEFA in liver tissue were decreased significantl y，while protein expression of PPAR α 15177460685@163.com was increased significantly （P＜0.05 or P＜0.01）. Some of the above indexes of HBOA high-dose group were 电话：0771-5302433。E-mail：junlin898@126.com significantly better than HBOA medium- and low-dose group（P＜0.05）. CONCLUSIONS ：HBOA has a certain improvement effect on non-alcoholic fatty liver disease in rats caused by high-fat diet ，and its mechanism may be related to improving lipid metabolism disorders ，anti-oxidative stress and up-regulating the expression of PPARα.
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Objective@#Investigate the effects of inducible ppp2r1a knockout on main physiological function in adult mice and study the mechanism.@*Methods@#Ppp2r1aflox/flox mice and CAGG-CreER mice were hybridized to obtain 20 CAGG-CreER ppp2r1aflox/flox and 20 mice in homozygous group. Two groups of mice were divided into 4 groups respectively, finally we got 8 groups with 5 mice in each group. Tamoxifen was injected intraperitoneally to acquire inducible ppp2r1a knockout mice. The knockout efficiency of PP2A Aα in vital organs was measured by Western blot. At 0, 2, 4 and 6 days after injection, we measured body weight, histopathological change, peripheral blood cell counts and blood biochemical. Real-time PCR was performed to measure expression of liver glucolipid metabolism genes.@*Results@#After tamoxifen injection for 6 days, the knockout efficiency of PP2A Aα in vital organs was 35%, 12%, 15%, 60%, 69% and 72%, respectively in heart, liver, spleen, lung, kidney and brain. After tamoxifen injection for 6 days, the weight of homozygous mice was lower than that of wild type mice, with values of (17.42±1.76) g and (21.69±1.82) g, respectively (P<0.05). Moreover, the activity level, abdominal and renal fat were significantly decreased in homozygous mice. Homozygous mice survived no more than 7 days. Compared with wild type mice, the organ coefficient of spleen of homozygous mice was decreased at the 6th day, with values of (0.59±0.10)% and (0.36±0.05)% respectively (P<0.05). Obvious spleen atrophy and marked decrease of nucleated cells were showed by performing HE staining. Tunel staining revealed increased apoptosis ratio of splenic lymphocytes in homozygous mice. The levels of alanine aminotransferase (ALT) and aspartate transaminase (AST) of homozygous mice were higher than wild type mice (P<0.05). The values of ALT and AST in homozygous mice were (153.68±62.80) U/L and (193.2±44.28) U/L. The corresponding values in wild type mice were (41.02±12.91) U/L and (69.40±9.55) U/L. The above results indicated that ppp2r1a knockout caused liver damage. Blood sugar level of homozygous mice was lower than in wild type mice (P<0.05), with values of (4.20±1.99) mmol/L and (8.88±0.65) mmol/L respectively. Plasma total cholesterol (TC), high density lipoprotein (HDL) and β-hydroxybutyric acid (β-HB) level of homozygous mice were higher than those of wild type mice (P<0.05). The values of TC, HDL and β-HB in homozygous mice were (3.12±0.39), (1.53±0.38) and (2.49±0.89) mmol/L. The corresponding values in wild type mice were (1.69±0.92), (0.78±0.50) and (0.45±0.30) mmol/L respectively. The above results indicated that ppp2r1a loss interfered glucose and cholesterol metabolism. In addition, we also found that the white blood cell count (WBC) and lymphocyte count (LYM) of homozygous mice were lower than in wild type mice (P<0.05). The values of WBC and LYM in homozygous mice were (1.88±0.89)×109/L and (0.92±0.37)×109/L respectively. The corresponding values in wild type mice were (3.91±0.80)×109/L and (2.74±0.52)×109/L respectively. The mRNA levels of glucose-6-phosphatase (G6P) and phosphoenolpyruvate carboxykinase (PEPCK) of homozygous were lower than wild type mice (P<0.05). The fold change of G6P and PEPCK in homozygous mice was 0.46±0.11 and 0.72±0.07 respectively. The corresponding fold change in wild type mice was 1.02±0.07 and 1.02±0.06 respectively.@*Conclusion@#Whole body ppp2r1a is essential for the survival of adult mice, due to the important role in maintaining the metabolism of glucose and cholesterol of liver.
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OBJECTIVE@#To investigate the effect of tea polyphenols on cardiac function in rats with diabetic cardiomyopathy, and the mechanism by which tea polyphenols regulate autophagy in diabetic cardiomyopathy.@*METHODS@#Sixty Sprague-Dawley (SD) rats were randomly divided into six groups: a normal control group (NC), an obesity group (OB), a diabetic cardiomyopathy group (DCM), a tea polyphenol group (TP), an obesity tea polyphenol treatment group (OB-TP), and a diabetic cardiomyopathy tea polyphenol treatment group (DCM-TP). After successful modeling, serum glucose, cholesterol, and triglyceride levels were determined; cardiac structure and function were inspected by ultrasonic cardiography; myocardial pathology was examined by staining with hematoxylin-eosin; transmission electron microscopy was used to observe the morphology and quantity of autophagosomes; and expression levels of autophagy-related proteins LC3-II, SQSTM1/p62, and Beclin-1 were determined by Western blotting.@*RESULTS@#Compared to the NC group, the OB group had normal blood glucose and a high level of blood lipids; both blood glucose and lipids were increased in the DCM group; ultrasonic cardiograms showed that the fraction shortening was reduced in the DCM group. However, these were improved significantly in the DCM-TP group. Hematoxylin-eosin staining showed disordered cardiomyocytes and hypertrophy in the DCM group; however, no differences were found among the remaining groups. Transmission electron microscopy revealed that the numbers of autophagosomes in the DCM and OB-TP groups were obviously increased compared to the NC and OB groups; the number of autophagosomes in the DCM-TP group was reduced. Western blotting showed that the expression of LC3-II/I and Beclin-1 increased obviously, whereas the expression of SQSTM1/p62 was decreased in the DCM and OB-TP groups (P<0.05).@*CONCLUSIONS@#Tea polyphenols had an effect on diabetic cardiomyopathy in rat cardiac function and may alter the levels of autophagy to improve glucose and lipid metabolism in diabetes.
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Animals , Male , Rats , Autophagy , Beclin-1 , Blood Glucose , Body Weight , Diabetic Cardiomyopathies , Drug Therapy , Pathology , Lipids , Blood , Myocardium , Pathology , Polyphenols , Pharmacology , Rats, Sprague-Dawley , Tea , ChemistryABSTRACT
Objective To investigate the protective effects of Toona sinensis leaf extract on the retina of rats with high-fat diet and the expression of B-cell lymphoma (Bcl-2) and Bcl-2 associated x protein (Bax).Methods Together 24 male SD rats were randomly divided into normal group (N group),hyperlipidemia model group (HF group) and hyperlipidemia model + toona sinensis leaf extract (HF + TSLE group),and then hyperlipidemia model was induced by fed high-fat diet in the latter two groups;after 8 weeks,the model was confirmed to be successful,and the rats in HF + TSLE group were fed with TSLE solution for 4 weeks continuously,and rats in N group and HF group were given the same dose of physiological saline.At the end of the twelfth week,all rats were followed by the examination of flash electroretinogram (FERG),serum lipid total cholesterol (TC),triglyceride (TG),low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C).Then,HE staining was performed in the retinas,the expression of Bcl-2 and Bax was detected by immunohistochemistry and Western blotting for the analysis of the correlation between the expression level of apoptotic protein Bax and the abnormal function of FERG.Results In HF group,the content of HDL-C decreased,and the contents of TC,TG and LDL-C were higher than those in N group,and the differences were statistically significant (all P ＜ 0.05).The contents of TC,TG and LDL-C in HF + TSLE group were lower than those in HF group,but the content of HDL-C was significantly increased,and the differences were statistically significant (all P ＜ 0.05).The content of HDL-C in HF + TSLE group was lower than that in N group,while the contents of TC,TG and LDL-C were higher than those in N group,and the differences were not statistically significant (all P ＞0.05).The difference of a wave latency between the three groups was statistically significant (P ＜ 0.05),and the latency of a wave in HF group was longer than that in N group,while HF + TSLE group was shorter than HF group,and the difference was statistically significant (P ＜ 0.05),but HF + TSLE group was longer than N group,and the difference was not statistically significant (P ＞ 0.05).Moreover,there was no significant difference in the incubation period of b wave in the three groups (P ＞ 0.05);and there was no significant difference in the amplitude of a wave and b wave in the three groups (all P ＞ 0.05).In addition,HF group had lower expression level of Bcl-2 and overexpression of Bax than N group.The expression level of Bcl-2 increased and Bax expression level decreased significantly in HF + TSLE group,and the expression level of Bax was positively correlated with the latency of a wave and b wave (all P ＜ 0.05),but was not correlated with amplitude of a wave and b wave (all P ＞ 0.05).Conclusion TSLE has an important role in the retina of rats with abnormal lipid metabolism,and it may play a protective role by regulating the expression of Bcl-2 and Bax.
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AIM:To investigate the effect of gestational diabetes mellitus ( GDM) on glucose-lipid metabolism in the offspring mice and the underlying mechanisms .METHODS:Wild-type female mice were intraperitoneally injected with streptozotocin at 30 mg/kg in the second trimester of pregnancy to establish GDM model .Normal saline was used as control.F1 offspring mice were fed for 8 weeks after birth.The blood glucose and lipid levels were detected randomly .The mRNA levels of p300 and p300/CBP-associated factor ( PCAF) were detected by qPCR .The expression of peroxisome pro-liferator-activated receptor-γ( PPAR-γ) , glucose transporter typer 4 ( GLUT-4 ) and medium-chain acyl-CoA dehydroge-nase ( MCAD) at mRNA and protein levels was determined by qPCR and Western blot .ChIP-qPCR was employed to ana-lyze the binding status of p 300 with the promoter of PPAR-γand the acetylation level of histone H 3 in the promoter region of PPAR-γ.RESULTS:Blood glucose and total cholesterol levels were significant increased in the offspring mice ( P<0.05).The expression levels of p300, PPAR-γ, GLUT-4 and MCAD were decreased compared with the control group (P<0.05).Binding affinity of p300 with the promoter of PPAR-γwas reduced (P<0.05).The level of acetylated his-tone H3 in the promoter region of PPAR-γwas decreased significantly ( P<0.05) .CONCLUSION:Regulation of PPAR-γexpression by p300 may induce glucose-lipid metabolism disorder in the cardiomyocytes of GDM offspring mice .
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AIM: To investigate whether inactivation of extracellular signal-regulated kinase 1/2 ( Erk1/2 ) will affect the function of fibroblast growth factor 21 (FGF21) to regulate glucose and lipid metabolism .METHODS:Male db/db mice (8 weeks old) were treated with U0126 (an inhibitor of Erk1/2 kinase) for 1 week, and then treated with re-combinant human FGF21 protein and adenovirus-mediated FGF21 (Ad-FGF21).The profile changes of blood glucose and blood lipid were evaluated at 120 min or 4 weeks after FGF21 administration.Meanwhile, the molecular mechanism was ex-plored by in vitro study.RESULTS: Treatment of db/db mice with recombinant human FGF21 protein significantly re-duced blood glucose and triglyceride levels at 120 min after FGF21 administration , but these changes were comparable in U0126-treated mice .Furthermore , abnormal glucose and triglyceride levels , and glucose and insulin tolerance were strong-ly improved in db/db mice as accompanied with decreasing body fat content after 4 weeks of ad-FGF21 administration .In-terestingly, treatment with or without U0126 did not influence these effects of FGF21.Mechanically, treatment with Ad-FGF21 significantly upregulated the protein levels of p-Erk1/2 and peroxisome proliferator-activated receptor γ( PPARγ) as well as the expression of adiponectin at mRNA and protein levels in adipose tissues .However , treatment with or without U0126 did not change the profiles .On the other hand , in vitro experiments also indicated that treatment of adipocytes with recombinant human FGF 21 protein significantly activated Erk 1/2 phosphorylation , and upregulated the expression levels of PPARγand adiponectin (P<0.05).However, pre-administration of U0126 did not affect the profiles.CONCLUSION:Pharmaceutical inactivation of Erk 1/2 by U0216 does not affect the biological function of FGF 21 to regulate blood glucose balance and improve abnormal blood lipids in vivo.
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Objective To detect the changes of serum lipid levels in diabetic peripheral neuropathy patients,investigate the relationship between ApoB and HOMA-IRI and diabetic peripheral neuropathy.Methods One hundred and eighty-two patients with type 2 diabetes mellitus admitted to the medical department of Xuanwu Hospital Capital Medical University from January 2015 to August 2016 were enrolled in this study.All patients underwent EMG detection,the MCV of bilateral median nerve,tibial nerve and common peroneal nerve,and the SCV of median nerve,ulnar nerve and sural nerve.According to the detection results and symptoms and signs,the subjects were divided into type 2 diabetic peripheral neuropathy group (DPN,86 cases) and type 2 diabetic non peripheral neuropathy group (NDPN,96 cases).The general demographic data of the two groups was recorded,including TC,TG,HDL-C,LDL-C,FBG,HaBlc,FINS,UA,UAE and HOMA-IRI,to analyze the relationship between the nerve conduction velocity in type 2 diabetes patients with peripheral neuropathy and HDL-C,LDL-C,FINS,HbAlc,ApoB,HOMA-IRI.Results The course of disease in patients with type 2 diabetic peripheral neuropathy ((9.53 + 2.38) years,UAE (22.24) mg/L) was higher than that in patients with type 2 diabetic non peripheral neuropathy ((6.37 + 1.59) years and UAE (9.83) mg/L);FINS and HOMA-IRI levels in the DPN group were lower than those in the NDPN group ((16.33±2.33) vs.(35.16±5.02),4.94 vs.15.27,t=10.629,4.459,31.842,3.128,P<0.05);the level of TG,LDL-C and ApoB in patients with type 2 diabetic peripheral neuropathy was higher than those in patients with type 2diabetic non peripheral neuropathy,and the difference was statistically significant (P<0.05);the disorder of lipid metabolism in the DPN group was serious,whose occurrence rate was higher compared with the NDPN group (P<0.05);the MCV of median nerve was negatively correlated with ApoB (r=-0.278,P=0.041),SCV was positively correlated with HDL-C (r=0.425,P=0.002);MCV of tibial nerve was positively correlated with HDL-C (r=0.335,P=0.031),SCV of ulnar nerve was positively correlated with HDL-C (r=0.425,P=0.004) and FINS (r=0.387,P=0.006),negatively correlated with HOMA-IRI (r=-0.405,P=0.008);sural nerve SCV was positively correlated with HDLD-C (r=0.532,P=0.001),and HbAlc (r=-0.383,P=0.005),negatively correlated with LDL-C (r=-0.361,P=0.018).Conclusion Nerve conduction velocities in patients with type 2 diabetic peripheral neuropathy were associated with HDL-C,LDL-C,FINS,HbAlc,ApoB,and HOMA-IRI.
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Objective To analyze the morbidity of the old people with hypertension and metabolic syndrome (MS),the characteristics of MS components distribution,and correlation hypertension and MS.Methods 438 old patients over 60 with hypertension were selected randomly from cheek-up crowd in the physical examination center of Affiliated Zhongshan Hospital of Dalian University in 2013.Abdominal girth,height,body mass were measured,and then calculated BMI.The indicators such as FPG,TC,TG,HDL-C,LDL-C were detected and analyzed.Results The total morbidity of MS in the old people with hypertension was 37.7％,39.0％ from male people,36.7％ from female people,and there was no difference between genders(x2 =0.46,P ＞ 0.05).The level of BMI,abdominal girth,FPG,and TG in the old people with MS were higher than the people without MS(t =4.83,8.53,5.08,7.29,all P ＜0.05),and HDL-C was lower than the people without MS(t =-9.67,P ＜ 0.05).The level of FPG in women was higher than that in men apparently(x2 =5.82,P ＜ 0.05),and the level of HDL-C was lower than that in men apparently (x2 =8.73,P ＜ 0.01).The risk factors to MS include BMI,abdominal girth,FPG,TG (OR =2.139,1.106,2.156,2.315,all P ＜0.05),and HDL-C is protective factor to MS(OR =0.039,P ＜0.05).Conclusion Hypertension might increase MS morbidity of old patients.Hypertension related with MS closely.The risk factors include BMI,abdominal girth,FPG,TG,on the other hand HDL-C is protective factor to MS.
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Objective To compare the endocrine and metabolic parameters between patients suffering from polycystic ovary syndrome (PCOS) with or without subclinical hypothyroidism.Methods One hundred and fifty-six PCOS patients and 47 healthy controls were enrolled.Height,weight,waist circumference,and hip circumference were measured and recorded.Fasting blood samples were collected for measuring luteinizing hormone (LH),follicular stimulating hormone (FSH),total testosterone,prolactin,estrogen,sex hormone binding globulin (SHBG),thyroidstimulating hormone (TSH),free triiodothyronine (FT3),free thyroxine (FT4),blood glucose,serum insulin,triglycerides,total cholesterol,low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol (HDL-C).Body mass index,waist-to-hip ratio,LH-to-FSH ratio,and free androgen index (FAI) were calculated.Homeostasis model assessment of insulin resistance (HOMA-IR) and β cell function (HOMA-β) were assessed.All patients underwent ultrasound for diagnosing polycystic ovary.All the patients were subdivided into two groups in terms of TSH value:subclinical hypothyroidism group with TSH level ≥4.2 μIU/ml and non-subclinical hypothyroidism group with TSH level＜4.2 μIU/ml.The differences in endocrine and metabolic parameters were compared between two subgroups.Results Compared with healthy controls,the PCOS patients had significantly higher body mass index,waist-to-hip ratio,LH,LH-to-FSH ratio,total testosterone,FAI,TSH,and lower SHBG (all P＜0.05).The other indexes were not different between two groups (P＞0.05).24.4％ PCOS patients were diagnosed as cases of subclinical hypothyroidism.TSH,prolactin,and triglycerides levels were higher in PCOS patients with subclinical hypothyroidism than those without (P＜0.01).Whereas estrogen,FT3,FT4 were significantly lower(P＜0.01).The differences of other parameters were not significant between two groups(P＞0.05).The results of correlation analysis and TSH quartiles showed no significant linear correlation between TSH and sex hormones,lipids,insulin resistance indices (P＞0.05).Conclusions The incidence of subclinical hypothyroidism in all PCOS patients is 24.4％.Prolactin and triglycerides levels were higher in PCOS patients with subclinical hypothyroidism than those without.Whereas estrogen,FT3,FT4 were significantly lower.
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Objective To investigate the changes of serum leptin levels and the influential factors in maintenance peritoneal dialysis patients.Methods Seventy-six peritoneal dialysis patients were chosen at the time before,and 3 months,6 months,12 months,18 months and 24 months after they began the peritoneal dialysis therapy,to examine body mass index (BMI),triceps skinfold thickness (TSF),abdominal circumference,homeostasis model assessment of insulin resistance (HOMA-IR),the plasma lipid profile,and leptin in the same situation.Results For 24 months,these patients showed higher serum leptin level than the values before commencing peritoneal dialysis treatment (P ＜ 0.01).The level of leptin was positively correlated with the BMI(r =0.412,P ＜ 0.01),TSF(r =0.308,P ＜ 0.01),abdominal circumference(r =0.284,P ＜ 0.01),HOMA-IR(r =0.184,P ＜ 0.01) and TG(r =0.288,P ＜ 0.01),negatively corelated with the high-density lipoprotein cholesterol(HDL-C)(r =-0.285,P ＜ 0.01).Multiple logistic regression analysis showed that BMI (β =0.339,P ＜ 0.01),TGβ =0.157,P ＜ 0.01) and HDL (β =-0.126,P ＜ 0.05)were significant predictive factors for the changes of serum leptin levels.Conclusion Leptin maybe involve in the occurrence and the development of cardiovascular events like other metabolic parameters in peritoneal dialysis therapy.
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A study was carried out on 51 patients with hypertension and blood lipid metabolism disorder at the Clinic Department and Heart-Renal-Joint Department in the Military Traditional Hospital and at the General Enterology Department in the Son Tay Hospital from Feb 2004 to Sept 2004. The patients were divided into two groups: study group included 2 patients using a TT2 traditional repice/day for 28 days; control group included 9 patients using Caporil 25mg x 2 tablets/day for 28 days. 50 white mousses of Swiss species were provided by The National Institute of Hygiene and Epidemiology. TT2 experiment showed no acute toxicity with experimental dose 50g/1kg of mouse weight. Boiling and drinking a TT2 traditional repice/day did not cause any side effects. TT2 helps to decrease blood pressure significantly in patients with hypertension and blood lipid metabolism disorder. After 4 weeks, the blood pressure level in patients using TT2 is as equivalent as in patients using Caporil 25mg x 2 tablets/day. TT2 improves symptoms of the both of disease type: dizzy, headache, neck pain, dyspepsia, insomnia, lose appetite, red face, red eyes and constipation.