ABSTRACT
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.
ABSTRACT
ObjectiveTo observe and compare the intervention effect of modified Cangfu Daotantang on glucose and lipid metabolism in simple obese children with phlegm dampness and stagnation. MethodA total of 60 children with simple obesity were randomly divided into two groups according to the simple randomization method of the random number table. The odd number was included in the test group， and the even number was included in the basic treatment group， with 30 cases in each group. On the basis of signing the informed consent notice， the treatment group was given modified Cangfu Daotantang combined with basic treatment， while the control group was only given basic treatment. After three months of treatment， the body mass index （BMI）， glucose and lipid metabolism level ［total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， fasting plasma glucose （FPG）， fasting insulin （FINS）， and homeostasis model assessment-insulin resistance （HOMA-IR）］， the change in the total score of traditional Chinese medicine （TCM） syndromes， and the effective rate of treatment were observed and compared. ResultAfter treatment， the BMI of the observation group and the control group decreased significantly （P<0.01）. Compared with the control group， the BMI level in the observation group decreased significantly （P<0.05）. After treatment， the levels of TC， TG， and LDL-C in the observation group and the control group decreased significantly （P<0.01）. Compared with the control group， the levels of TC， TG， and LDL-C in the observation group decreased significantly （P<0.05）. In addition， the level of TC in the observation group improved significantly compared with that in the control group （P<0.01）. The levels of FPG， FINS， and HOMA-IR in the observation group and the control group were significantly lower than those before treatment （P<0.05）. After treatment， compared with the control group， the levels of FPG， FINS， and HOMA-IR in the observation group were significantly reduced （P<0.05）. The level of FPG in the observation group was significantly improved compared with that in the control group （P<0.01）. After treatment， the total score of TCM syndromes in the two groups decreased significantly （P<0.01）. Compared with the control group， the total score of TCM syndromes in the observation group was lower （P<0.01）. After treatment， the total effective rate of treatment was 86.67% （26/30） in the observation group and 73.33% （22/30） in the control group. By rank sum test， the total effective rate of the observation group was better than that of the control group （Z=-2.100， P<0.05）. ConclusionModified Cangfu Daotantang combined with basic treatment can effectively reduce the BMI of obese children and improve their glucose and lipid metabolism. It has good clinical effects and high clinical application value， which is worth further in-depth research and promotion.
ABSTRACT
ObjectiveTo investigate the different effects of Yunvjian with or without Achyranthis Bidentatae Radix on glucose and lipid metabolism and inflammatory response in diabetic rats with the syndrome of Yin deficiency and internal heat. MethodThe rat model of diabetes due to Yin deficiency and internal heat was established by feeding with a high-sugar and high-fat diet and injection of thyroxine and streptozotocin. The successfully modeled rats were randomized into model control， Yunvjian without Achyranthis Bidentatae Radix （11.8 g·kg-1）， Yunvjian with Achyranthis Bidentatae Radix （12.8 g·kg-1）， and Achyranthis Bidentatae Radix （1.0 g·kg-1） groups （n=10）， and another 10 rats were taken as the normal control group. Each group was administrated with corresponding drugs or saline by gavage for 28 days. The fasting blood glucose （FBG）， fasting insulin （FINS）， total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） in rats were measured. Enzyme-linked immunosorbent assay was employed to determine the levels of cyclic adenosine monophosphate （cAMP）， cyclic guanosine monophosphate （cGMP）， triiodothyronine （T3）， thyroxine （T4）， interleukin （IL）-1β， IL-6， tumor necrosis factor （TNF）-α， and C-reactive protein （CRP） in the serum. The histopathological changes of the liver were observed. The expression of lipoxygenase-2 （COX-2） was detected by immunofluorescence. The mRNA levels of nuclear transcription factors-κB （NF-κB）， monocyte chemotactic protein-1 （MCP-1）， and intercellular adhesion molecule-1 （ICAM-1） were determined by real-time polymerase chain reaction （Real-time PCR）.Western blot was employed to determine the protein levels of NF-κB in hibitory protein（IκB） kinase β （IKKβ）， IκBα， and phosphorylated IκBα （p-IκBα） in the liver and the protein levels of NF-κB in the cytoplasm and nucleus. ResultCompared with the normal group， the model group showed elevated levels of FBG， FINS， insulin resistance index， TC， TG， LDL-C， cAMP， T3， T4， IL-1β， IL-6， TNF-α， and CRP， up-regulated mRNA levels of NF-κB， MCP-1， and ICAM-1， and up-regulated protein levels of COX-2， p-IκBα， and nuclear NF-κB （P<0.01）. Compared with the model group， Yunvjian without Achyranthis Bidentatae Radix lowered the levels of FBG， FINS， insulin resistance index， TC， TG， LDL-C， cAMP， T3， T4， IL-1β， IL-6， TNF-α， and CRP， down-regulated the mRNA levels of NF-κB， MCP-1， and ICAM-1， and down-regulated the protein levels of COX-2， p-IκBα and nuclear NF-κB （P<0.05， P<0.01）. Compared with the Yunvjian without Achyranthis Bidentatae Radix， Yunvjian with Achyranthis Bidentatae Radix showed lowered levels of FBG， FINS， insulin resistance index， and inflammatory cytokines， down-regulated mRNA levels of NF-κB， MCP-1， and ICAM-1， and down-regulated protein levels of p-IκBα and nuclear NF-κB （P<0.05， P<0.01）. ConclusionAchyranthis Bidentatae Radix can enhance the performance of Yunvjian in reducing blood glucose and inhibiting inflammation in diabetic rats with the syndrome of yin deficiency and internal heat by down-regulating the IKK/IκB/NF-κB signaling pathway.
ABSTRACT
ObjectiveBased on network pharmacology and transcriptomics， the mechanism of Zishen Qinggan prescription （ZSQGF） in improving glucose and lipid metabolism in type 2 diabetes （T2DM） model rats was explored. MethodBased on network pharmacology analysis of the differential genes between ZSQGF and T2DM， gene ontology（GO）analysis and Kyoto encyclopedia of genes and genomes（KEGG） analysis were conducted， and molecular docking analysis was used to verify the binding between components and targets. A T2DM rat model was established by high-fat feeding and injection of streptozotocin （STZ）. The rats were randomly divided into the control group， model group， metformin （Met， 72 mg·kg-1） group， and ZSQGF high-， medium-， and low-dose groups （ZSQGF-H， ZSQGF-M， and ZSQGF-L， with 4.8， 2.4， and 1.2 g·kg-1 raw drug in the solution）. The living status of rats was monitored and the levels of total cholesterol （TC）， total triglycerides （TG）， high density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） in rat serum were detected. The liver tissues were subjected to Hematoxylin eosin（HE） staining and oil red O staining. The differential genes were analyzed through transcriptomics， GO and KEGG analysis， and the protein-protein interaction（PPI） network was obtained to screen key targets. With network pharmacology and transcriptomics analysis results， the protein pathways were identified. The expression levels of nuclear factor-κB （NF-κB）， matrix metalloproteinase（MMP）-1 and MMP-9 proteins in liver tissues were detected by Western blot. The mRNA expression of B-cell lymphoma-2（Bcl-2） modifying factor（BMF）， nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4）， and fatty acid synthase（FASN） was detected by real-time polymerase chain reaction（Real-time PCR）. The expression of MMP-1 and MMP-9 in the liver was detected by immunofluorescence staining. ResultTranscriptomics and network pharmacology analysis suggested that ZSQGF may protect the liver through the glucose and lipid metabolism pathway and the inflammation pathway. Experiments showed that after 8 weeks of administration， the body weight， blood sugar， serum indicators， and pathological staining results of rats were improved. Western blot results indicated a decrease in the relative expression levels of NF-κB， MMP-1 and MMP-9 proteins in the liver. Real-time PCR results showed a decrease in the transcriptional expression of BMF， NOX4， and FASN in the ZSQGF-H group， while immunofluorescence staining results present decreased expression of MMP-1 and MMP-9 in the ZSQGF groups. ConclusionZSQGF can improve the glucose and lipid metabolism by inhibiting the expression of FASN， reducing lipid synthesis， and regulating the NF-κB signaling pathway.
ABSTRACT
ObjectiveTo investigate the effect of Gegen Qinliantang on glucose and lipid metabolism in the rat model of catch-up growth （CUG） induced by a high-fat diet and the underlying mechanism. MethodA total of 60 SD rats were randomized into a normal control group （n=18） and a modeling group （n=42）. The rat model of CUG was established with a restricted diet followed by a high-fat diet， and the changes of general status and body weight were observed. The levels of fasting blood glucose （FBG）， fasting insulin （FINS）， triglyceride （TG）， and total cholesterol （TC） were measured in 6 rats in each group at the end of the 4th and 8th week， respectively. The homeostasis model assessment of insulin resistance index （HOMA-IR） was calculated， and the insulin sensitivity and body composition changes of CUG rats were evaluated. The successfully modeled rats were assigned into 6 groups： normal control， model， high-， medium-， and low-dose Gegen Qinliantang （2.5， 5， 10 g·kg-1）， and pioglitazone （3.125 mg·kg-1）. The rats were administrated with corresponding drugs by gavage for 6 weeks， and the normal control group and model group were administrated with the same amount of normal saline. During the experiment period， the changes of body weight were recorded， and the FBG， FINS， HOMA-IR， TG， and TC were determined at the end of the experiment. Hematoxylin-eosin （HE） staining was employed to observe the pathological changes of skeletal muscle in rats. The levels of reactive oxygen species （ROS） and malondialdehyde （MDA） in the skeletal muscle were measured strictly according to the manuals of the reagent kits. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was performed to measure the mRNA levels of silencing information regulator 1 （SIRT1）， peroxisome proliferator-activated receptor-gamma coactivator1α （PGC1α）， and nuclear respiratory factor 1 （Nrf1） in the skeletal muscle. Western blot and immunohistochemistry were employed to assess the expression of SIRT1， PGC1α， and Nrf1 in the skeletal muscle. ResultCompared with the normal control group， the model group presented elevated levels of FBG， FINS， TG， and TC （P<0.05， P<0.01）， increased HOMA-IR （P<0.01）， increased diameter of muscle fibers and adipocytes between muscle cells in the skeletal muscle， rising levels of ROS and MDA in the skeletal muscle （P<0.01）， and down-regulated mRNA and protein levels of SIRT1， PGC1α， and Nrf1 （P<0.05， P<0.01）. Compared with the model group， Gegen Qinliantang （especially the medium and high doses） and pioglitazone decreased the body weight， FINS， HOMA-IR， and TG （P<0.05， P<0.01） and reduced interstitial components such as intermuscular fat in the skeletal muscles and the diameter of muscle fibers. Furthermore， the drugs lowerd the levels of ROS and MDA （P<0.05， P<0.01） and up-regulated the mRNA and protein levels of SIRT1， PGC1α， and Nrf1 （P<0.05， P<0.01） in the skeletal muscle. ConclusionGegen Qinliantang can ameliorate the glucose and lipid metabolism disorders and insulin resistance in CUG rats by regulating the SIRT1/PGC1α/Nrf1 signaling pathway.
ABSTRACT
Intestinal flora imbalance and abnormal glucose and lipid metabolism are important risk factors and pathological mechanisms of colorectal polyps. "Spleen deficiency and dampness accumulation" is the core pathogenesis of colorectal polyps. The imbalance of intestinal flora is related to spleen deficiency, and the application of Chinese herbs for invigorating spleen is helpful to the recovery of intestinal flora balance. Abnormal glucose and lipid metabolism is related to dampness accumulation, and it is effective to treat it with bitter and spicy herbs or spleen-invigorating and dampness-eliminating herbs. The interaction between intestinal flora imbalance and abnormal glucose and lipid metabolism changes intestinal microenvironment, damages intestinal epithelial cells, causes abnormal proliferation of intestinal stem cells and leads to colorectal polyps, which is consistent with the pathogenesis of spleen deficiency and dampness accumulation in Traditional Chinese Medicine. Thus, we tried to explore the biological connotation of the pathogenesis of "spleen deficiency and dampness accumulation" of colorectal polyps from the perspective of the interaction of intestinal flora and glucose and lipid metabolism, in order to provide reference for identifying high-risk population and analyzing the therapeutic mechanism of compound prescription for invigorating spleen and removing dampness.
ABSTRACT
OBJECTIVES@#To observe the effects on the glucose-lipid metabolism and the expression of zinc-α2-glycoprotein (ZAG) and glucose transporter 4 (GLUT4) in the femoral quadriceps and adipose tissue after electroacupuncture (EA) at "Pishu" (BL 20), "Weiwanxiashu" (EX-B 3), "Zusanli" (ST 36) and "Sanyinjiao" (SP 6) in the rats with diabetes mellitus type 2 (T2DM), so as to explore the effect mechanism of EA in treatment of T2DM.@*METHODS@#Twelve ZDF male rats were fed with high-sugar and high-fat fodder, Purina #5008 for 4 weeks to induce T2DM model. After successfully modeled, the rats were randomly divided into a model group and an EA group, with 6 rats in each one. Additionally, 6 ZL male rats of the same months age were collected as the blank group. The rats in the EA group were treated with EA at bilateral "Pishu" (BL 20), "Weiwanxiashu" (EX-B 3), "Zusanli" (ST 36) and "Sanyinjiao" (SP 6), with continuous wave, 15 Hz in frequency, and 2 mA in intensity. The electric stimulation lasted 20 min each time. EA was delivered once daily, 6 times a week for 4 weeks. Separately, the levels of fasting blood glucose (FBG) was measured before modeling, before and after intervention, and the body mass of each rat was weighted before and after intervention. After intervention, the levels of the total cholesterol (TC), triacylglycerol (TG) and free fatty acid (FFA) in serum were detected using enzyme colorimetric method; and the levels of the serum insulin (INS) and ZAG were detected by ELISA. Besides, the insulin sensitivity index (HOMA-ISI) was calculated. With Western blot technique adopted, the protein expressions of ZAG and GLUT4 in the femoral quadriceps and adipose tissue were determined.@*RESULTS@#After intervention, compared with the blank group, the levels of FBG and body mass, and the levels of serum TC, TG, FFA and INS increased (P<0.01), while HOMA-ISI decreased (P<0.01); the level of ZAG in the serum and the protein expressions of ZAG and GLUT4 in the femoral quadriceps and adipose tissue dropped (P<0.01) in the model group. In the EA group, compared with the model group, the levels of FBG and body mass, and the levels of serum TC, TG, FFA and INS were reduced (P<0.01), and HOMA-ISI increased (P<0.01); the level of ZAG in the serum and the protein expressions of ZAG and GLUT4 in the femoral quadriceps and adipose tissue increased (P<0.01, P<0.05).@*CONCLUSIONS@#Electroacupuncture can effectively regulate glucose-lipid metabolism, improve insulin resistance and sensitivity in the rats with T2DM, which is associated with the modulation of ZAG and GLUT4 expression in the skeletal muscle and adipose tissue.
Subject(s)
Rats , Male , Animals , Glucose/metabolism , Electroacupuncture , Rats, Sprague-Dawley , Diabetes Mellitus, Type 2/therapy , Lipid Metabolism , Triglycerides , Adipose Tissue/metabolism , Acupuncture PointsABSTRACT
ObjectiveTo investigate the mechanism of Zuogui Jiangtang Qinggan prescription （ZJQP） in improving glucose and lipid metabolism in loss of skeletalmuscle-specific insulin-like growth factor-1 receptor function （MKR） mice with type 2 diabetes mellitus （T2DM） and non-alcoholic fatty liver disease （NAFLD）. MethodNAFLD was induced by high-fat diet feeding for 8 weeks in MKR mice， which were randomly divided into model group， metformin group （0.067 g·kg-1）， and ZJQP high and low-dose groups（14.8， 7.4 g·kg-1）. Ten FVB mice of the same age were used as the normal group. After 8 weeks of drug treatment， the oral glucose tolerance test （OGTT） was performed， the serum was taken to detect triacylglycerol （TG） and total cholesterol （TC）， and the wet weight of the mouse liver was weighed. Haematoxylin-eosin （HE） staining and oil red O staining were performed to assess histopathology of liver. The mRNA expression and protein expression of Fork head box protein O1 （FoxO1）， phosphoenolpyruvate carboxykinase （PEPCK）， glucose-6-phosphatase （G6Pase）， and apolipoprotein C3 （ApoC-Ⅲ） in liver tissues were detected by real-time fluorescent quantitative PCR （Real-time PCR） and Western blot， respectively. ResultAs compared with the normal group， the levels of fasting blood glucose， liver index， serum TG， TC， and OGTT of mice in the model group increased significantly （P<0.01）. As compared with model group， the fasting blood glucose and liver index of the mice in the metformin group and the ZJQP group decreased significantly （P<0.01）， the serum levels of TG and TC in the high-dose ZJQP group decreased significantly （P<0.05，P<0.01）， and the OGTT of mice in the metformin group and the high-dose ZJQP group improved （P<0.05）. In histopathology， as compared with the normal group， mice in the model group showed decreased lipid droplets and vacuoles in hepatocytes， and their volumes became larger. Compared with the model group， the ZJQP group and metformin group showed that the lipid droplets in liver tissues were reduced， the vacuoles in liver cells were reduced， and the volume was smaller. At the molecular level， as compared with the normal group， the mRNA and protein levels of FoxO1， PEPCK， G6Pase， and ApoC-Ⅲ in liver tissues of mice in the model group were significantly up-regulated （P<0.01）. As compared with the model group， the mRNA and protein levels of FoxO1， PEPCK， G6Pase， and ApoC-Ⅲ in the ZJQP group was significantly decreased （P<0.01）. ConclusionZJQP can improve the glucose and lipid metabolism of T2DM with NAFLD and repair the pathological damage of liver， which may be through regulating the expression of FoxO1， PEPCK， G6Pase， ApoC-Ⅲ-related proteins in liver tissues to achieve the effects of regulating lipid， lowering glucose， and delaying hepatic steatosis.
ABSTRACT
Objective To explore the characteristics of blood uric acid levels and its correlation with calcium and phosphorus levels, and glucose and lipid metabolism in obese adolescents in weight-loss training camps. Methods In this study, 357 obese adolescents aged 12-18 were selected as the research subjects, and 135 normal-weight adolescents were selected as the controls. The body shape and blood uric acid characteristics of the subjects were measured and analyzed. Further, 59 subjects were selected from the obese adolescents for blood calcium, blood phosphorus and glucose and lipid metabolism index tests to analyze the correlation between blood uric acid level and calcium, phosphorus, and glucose and lipid metabolism indicators. Results The average blood uric acid level of obese adolescents was (527.12±122.94)μmol/L, (566.58±122.51)μmol/L for boys, and (468.35±97.79)μmol/L for girls. The blood uric acid level of the obesity group was significantly higher than that of the control group (P<0.001 for boys, P<0.05 for girls), and it was higher in boys than in girls (P<0.01). Obese adolescents with high uric acid accounted for 73.39%. The HOMA-IR of obese adolescents was 5.79±3.04. The blood uric acid level was significantly correlated with blood calcium, total cholesterol, and low-density lipoprotein cholesterol (P<0.05). Gender and low-density lipoprotein cholesterol were the main influencing factors of blood uric acid (P<0.05). Conclusion Obese adolescents have high blood uric acid levels, low calcium and high phosphorus in the body, and a higher incidence of insulin resistance. There exists a positive correlation between the blood uric acid level and the body's calcium and phosphorus metabolism and glucose and lipid metabolism in obese adolescents. Clinical monitoring of lipid metabolism indicators such as low-density lipoprotein has certain reference value for the prevention and treatment of hyperuricemia.
ABSTRACT
ObjectiveTo explore the effects of Baihu Jia Renshen Tang （BHRS） on the related molecules on the phosphatidylinositol-3-kinase/protein kinase B（PI3K/Akt）signaling pathway in the liver of MKR diabetic model mice. MethodThirty 6-week-old MKR mice were selected and fed on a high-fat diet for four weeks，followed by intraperitoneal injection of streptozotocin（STZ）for the diabetes model establishment. The model was properly induced in the case of the fasting blood glucose （FBG） of ≥11.1 mmol·L-1. After modeling，the mice were randomly divided into a model group，a BHRS group （12.09 g·kg-1·d-1），and a metformin group （0.065 g·kg-1·d-1），with 10 mice in each group. Ten FVB mice were assigned to the control group. The mice in the groups with drug intervention were continuously administered correspondingly for 28 days. After administration，the mice were sacrificed，followed by the oral glucose tolerance test （OGTT） and FBG detection. Serum very low-density lipoprotein（VLDL）content was determined by semi-quantitative enzyme-linked immunosorbent assay （ELISA）. Four indexes related to blood lipid were determined by the biochemistry analyzer. Liver tissues were subjected to pathological examination by hematoxylin-eosin（HE）staining. Western blot was used to detect the protein expression of PI3K，Akt，phosphorylated（p）-PI3K，p-Akt，forkhead box protein O1 （FoxO1），insulin receptor（InsR），and insulin receptor substrate-2（IRS-2） in liver tissues of mice. Real-time polymerase chain reaction（Real-time PCR） was used to detect the mRNA expression of PI3K，Akt，FoxO1，InsR，and IRS-2 in liver tissues of mice. ResultCompared with the control group，the model group showed poor general conditions，abnormal glucose tolerance （P<0.05），increased FBG （P<0.01），abnormal blood lipid metabolism，increased serum total cholesterol （TC），triglyceride（TG），low-density lipoprotein cholesterol（LDL-C），and VLDL （P<0.05），decreased level of high-density lipoprotein cholesterol（HDL-C）（P<0.05），fatty degeneration and obvious pathological changes of liver cells，reduced protein expression of PI3K，Akt，p-PI3K/PI3K，p-Akt/Akt，IRS-2，and InsR in liver tissues（P<0.05），increased protein expression of FoxO1（P<0.05），decreased mRNA expression of PI3K，Akt，IRS-2，and InsR in liver tissues （P<0.05），and increased FoxO1 mRNA expression（P<0.05）. Compared with the model group，the BHRS group showed improved general conditions and glucose and lipid metabolism （P<0.05），improved pathological state of liver cells，increased protein expression of PI3K，Akt，p-PI3K/PI3K，p-Akt/Akt，IRS-2，and InsR in liver tissues（P<0.05），decreased protein expression of FoxO1（P<0.05），increased mRNA expression of PI3K，Akt，IRS-2，and InsR in liver tissues （P<0.05），and reduced FoxO1 mRNA expression（P<0.05）. ConclusionBHRS can effectively reduce blood glucose，regulate blood lipid metabolism，and improve the pathological state of the liver in MKR diabetic mice，and its mechanism of action may be related to the regulation of the activity of molecules on the PI3K/Akt signaling pathway.
ABSTRACT
With the improvement of living standards and changes in working style, the prevalence of abnormal glucose and lipid metabolism in humans is increasing in modern society. Clinically, the related indicators are often improved by changing the lifestyle and/or taking hypoglycemic and lipid-lowering drugs, but there are no therapeutic drugs for disorders of glucose and lipid metabolism at present. Hepatitis C virus core protein binding protein 6(HCBP6) is a newly discovered target that can regulate triglyceride and cholesterol content according to level oscillations in the body, thereby regulating abnormal glucose and lipid metabolism. Relevant studies have shown that ginsenoside Rh_2 can significantly up-regulate the expression of HCBP6, but there are few studies on the effect of Chinese herbal medicines on HCBP6. Moreover, the three-dimensional structural information of HCBP6 has not been determined and the discovery of potential active components acting on HCBP6 is not rapidly advanced. Therefore, the total saponins of eight Chinese herbal medicines commonly used to regulate abnormal glucose and lipid metabolism were selected as the research objects to observe their effect on the expression of HCBP6. Then, the three-dimensional structure of HCBP6 was predicted, followed by molecular docking with saponins in eight Chinese herbal medicines to quickly find potential active components. The results showed that all total saponins tended to up-regulate HCBP6 mRNA and protein expression, where gypenosides showed the optimum effect on up-regulating HCBP6 mRNA and ginsenosides showed the optimum effect on up-regulating HCBP6 protein expression. Reliable protein structures were obtained after the prediction of protein structures using the Robetta website and the evaluation of the predicted structures by SAVES. The saponins from the website and literature were also collected and docked with the predicted protein, and the saponin components were found to have good binding activity to the HCBP6 protein. The results of the study are expected to provide ideas and methods for the discovery of new drugs from Chinese herbal medicines to regulate glucose and lipid metabolism.
Subject(s)
Humans , Glucose , Lipid Metabolism , Molecular Docking Simulation , Drugs, Chinese Herbal/pharmacology , Ginsenosides , Proteins , Saponins , RNA, MessengerABSTRACT
ObjectiveTo explore the effects and mechanisms of Kaiyu Zhongyutang on insulin resistance， glucose and lipid metabolism， psychological state， and embryo outcome in the infertile patients with polycystic ovary syndrome （PCOS） due to liver depression and kidney deficiency. MethodThe 126 infertile patients with PCOS due to liver depression and kidney deficiency who underwent in vitro fertilization-embryo transfer （IVF-ET） in the Department of Reproduction of the affiliated hospital of Nanjing university of Chinese medicine were randomly assigned into the observation （Kaiyu Zhongyutang + metformin） and control （metformin） groups. The two groups were compared in terms of traditional Chinese medicine （TCM） syndrome scores， body mass index （BMI）， glucose and lipid metabolism， homeostasis model assessment-insulin resistance （HOMA-IR）， interleukin （IL）-6， IL-8， C-reactive protein （CRP）， self-rating depression scale （SDS） score， self-rating anxiety scale （SAS） score， and clinical and laboratory scores of IVF after treatment. Result① After treatment， the observation group showed decreased scores of primary and secondary TCM syndromes and total TCM syndrome score （P < 0.05）， and the control group presented decreased scores of irritability and depression and total TCM syndrome score （P<0.05）. Compared with the control group， the observation group demonstrated reduced primary and secondary syndrome scores and total score after treatment （P<0.05）. ② After treatment， both groups showed decreased BMI， lowered levels of fasting insulin （FINS）， fasting plasma glucose （FPG）， cholesterol （TC）， triglyceride （TG）， low-density lipoprotein （LDL）， and HOMA-IR （P<0.05）， and elevated high-density lipoprotein （HDL） level （P<0.05）. Moreover， the observation group had lower BMI， FINS， FPG， TC， TG， LDL， and HOMA-IR and higher HDL than the control group （P<0.05）. ③ The treatment in both groups lowered the levels of IL-6， IL-8， and CRP and decreased SDS and SAS scores （P<0.05）. Moreover， the declines in the observation group were more obvious than those in the control group （P<0.05）. ④ Correlation analysis before treatment， IL-6， IL-8， and CRP had positive correlations with BMI， HOMA-IR， TC， TG， LDL， SDS， and SAS （P<0.05） and a negative correlation with HDL （P<0.05）. ⑤ The observation group showed reduced gonadotropin （Gn） using days and total Gn dose and higher two-pronuclear （2PN） fertilized oocytes， 2PN cleavage rate， normal fertilization rate， D3 transferable embryo number， D3 high-quality embryo number， high-quality embryo rate， and blastocyst formation rate than the control group （P<0.05）. ConclusionKaiyu Zhongyutang can treat PCOS patients by improving the emotional and reproductive functions and alleviating insulin resistance and glucose and lipid metabolism disorders. Moreover， it can reduce the Gn dose and Gn using days in the IVF process， improve the quality and maturity of eggs， increase the egg fertilization rate， enhance the potential of embryo development， and increase the rate of blastocyst formation by inhibiting inflammation.
ABSTRACT
Objective:To study the different effects of pre-pregnancy obesity (PO), excessive gestational weight gain (EGWG), pre-pregnancy obesity combined with excessive gestational weight gain (PO+EGWG) of maternal rats on glucose and lipid metabolism in neonatal offspring, and to explore the possible mechanisms.Methods:Animal models of PO, EGWG and PO+EGWG were established by feeding SD rats with high-fat diets at different periods. Thirty-six SD rats were randomly divided into four groups, with nine rats in each group. The control group had a normal diet before and during pregnancy. The PO group had a high-fat diet before pregnancy and a normal diet during pregnancy. The EGWG group had a normal diet before pregnancy and a high-fat diet during pregnancy. And the PO+EGWG group had a high-fat diet before and during pregnancy. The body weight of maternal rats before and during pregnancy and the birth weight of neonatal rats were recorded. Nine male neonatal rats in each group were selected, fasting blood glucose levels were detected by glucometer, fasting insulin levels were detected by enzyme-linked immunosorbent assay kit, hepatic triglyceride and cholesterol levels were detected by glycerol phosphate oxidase-peroxidase method, hepatic lipid deposition were observed by hematoxylin-eosin staining and oil red O staining. The mRNA levels of hepatic key genes in glucose metabolism pathway IR, IRS, AKT and lipid metabolism FASN, SREBP1c, PPARα were detected by reverse transcription-polymerase chain reaction analyses.Results:The pre-pregnancy weight of maternal rats in high-fat diet group before pregnancy (PO group and PO+EGWG group) was significantly higher than those in normal diet group (control group and EGWG group). The percentage of weight gain of maternal rats in high-fat diet group during pregnancy (EGWG group and PO+EGWG group) was significantly higher than those in normal diet group (control group and PO group) ( P<0.05). The birth weight of neonatal rats in PO group, EGWG group and PO+EGWG group were significantly higher than that in control group ( P<0.05), and the birth weight of neonatal rats in PO+EGWG group was the largest. The fasting glucose, insulin level and insulin resistance index of newborn rats in PO, EGWG and PO+EGWG groups were higher than those in the control group, and the mRNA levels of IR, IRS and AKT were lower than those in the control group, but the differences were not statistically significant ( P>0.05). The hepatic triglyceride and cholesterol contents and mRNA levels of FASN and SREBP1c were higher in the EGWG and PO+EGWG groups than those in the control group, and the mRNA level of PPARα was higher in the PO+EGWG group than in the control and PO groups, with statistically significant differences ( P<0.05). Conclusions:Animal models of PO, EGWG and PO+EGWG were successfully constructed by feeding SD rats with high-fat diets before pregnancy, during pregnancy, before and during pregnancy. PO+EGWG had the most significant effects on the birth weight and glucose and lipid metabolism in neonatal offspring. Compared with EGWG, PO had a relatively significant effect on glucose metabolism in neonatal offspring. And compared with PO, EGWG had a relatively significant effect on lipid metabolism in neonatal offspring. The effects of maternal obesity on glucose and lipid metabolism in neonatal offspring were considered to be related to the expression changes of genes in glucose and lipid metabolism.
ABSTRACT
Objective:To analyze the detective value of placental tissue resistin, human lipid carrier protein (LCN) and blood glucose and lipid metabolism in pregnant women with gestational diabetes mellitus (GDM) complicated with preeclampsia (PE) , providing guidance for the early treatment of GDM complicated with preeclampsia.Methods:96 pregnant women with GDM complicated with PE (GDM-PE group) admitted to Yantai Yantaishan Hospital from Jan. 2017 to Jan. 2020 were selected and retrospectively studied. According to the ratio of 2:1, the pure GDM pregnant women (GDM group) and 48 normal pregnant women (the control group) were selected. The placenta tissue resistin and LCN levels were determined by immunohistochemistry. Blood samples were collected to determine the glucose and lipid metabolism. The pregnancy outcomes of each group were compared and the relationship between resistin, LCN, glucose and lipid metabolism and GDM complicated with PE was analyzed.Results:Fasting blood-glucose (FBG) was (4.57±0.66) mmol/L in GDM group and (5.23±0.61) mmol/L in GMD-PE group. FINS (11.97±1.5) mIU/L, (15.12±3.52) mIU/L were higher than those of control group (4.11±0.23) mmol/L, (6.75±1.34) mIU/L ( P<0.05) . FBG, FINS, glycosylated hemoglobin (HbA1c) in GDM-PE group were higher than those in GDM group. TC) (6.71±1.63) mmol/L, triglyceride, TG (6.59±0.87) mmol/L was higher than that of control group (5.87±0.73) mmol/L, (4.57±0.59) mmol/L and GDM group (6.02±1.55) mmol/L, (4.71±0.63) mmol/L ( P<0.05) . high density lipoprotein cholesterol (HDL-C) (1.21±0.34) was lower than that of control group (1.54±0.39) and GDM group (1.55±0.43) ( P<0.05) . The positive rates of resistin 85.42%, 60.42%, LCN 81.25%, 56.25% in GDM-PE group and GDM group were higher than those in control group 39.58%, 31.25% ( χ2=32.096, 4.167; 34.975, 6.095, both P<0.05) . The positive rates of resistin and LCN in GDM-PE group were higher than those in GDM group ( χ2=11.322, 11.257, both P<0.01) . The gestational age of delivery in GDM-PE group was (37.11±2.06) weeks earlier than that in GDM group (38.21±1.75) weeks and control group (38.36±1.42) weeks ( F=9.836, P<0.05) . The birth weight of neonates (2 905.45±356.79) g was lower than that of control group (3 321.52±366.46) g and GDM group (3 425.14±269.87) g ( F=46.606, P<0.05) . Postpartum blood loss (415.34±126.75) ml was significantly higher than that of GDM group (338.65±105.63) ml and control group (298.42±75.26) ml ( F=19.932, P<0.05) . The preterm birth rate of 20.83% was higher than that of the GDM group (8.33%) and the control group (4.17%) ( χ2=9.075, P<0.05) . The postpartum blood loss of the GDM group was higher than that of the control group ( t=-2.148, P<0.05) . The incidences of fetal distress, premature rupture of membranes, fetal growth restriction and postpartum hemorrhage in GDM-PE group were higher than those in control group ( χ2=4.571, 6.867, 5.941, 5.123, P<0.05) . The protein expressions of resistin and LCN in placenta of pregnant women with GDM-PE were positively correlated with FBG, FINS, TC and TG ( r=0.517, 0.463, 0.559, 0.521, 0.485, 0.497, 0.557, 0.571, P<0.05) . Was negatively correlated with HDL-C ( r=-0.317, -0.357, P<0.05) . Conclusions:The positive rate of resistin and LCN in the placenta tissue of pregnant women with GDM complicated with PE is higher than that of GDM and normal pregnant women, their disorder of glucose and lipid metabolism is more obvious, and the incidence of adverse maternal and infant outcomes is higher. It is speculated that resistin and LCN may synergistically affect the metabolism of glucose and lipids causing adverse pregnancy outcomes in GDM complicated with PE.
ABSTRACT
Spexin is a new cytokine with a short peptide of 14 amino acids encoded by Ch12orf39, which can be identified by bioinformatics technology.The sequence of Spexin is widely expressed in various organs and is conserved during vertebrate evolution.The physiological effects of Spexin are getting increasing attention in recent years.The studies suggest Spexin plays multiple physiological functions, and the main ligands for biological effects are galanin receptor type 2 and galanin receptor type 3.Spexin palys an important biological role in energy metabolism and homeostasis, cardiovascular function and feeding behavior, and even can affect the regulation of pain and depression relief and reproductive function.This review aims to systemically summarize the Spexin and its related biological functions in metabolic diseases and feeding behavior.
ABSTRACT
Objective:To explore the pathogenesis of major depressive disorder(MDD) by comparing the serum glucose and lipid metabolism indicators, levels of glucagon-like peptide-1(GLP-1) in plasma and feces, and the content of specific intestinal flora ( Lactobacillus, Bifidobacterium) between patients with MDD who were diagnosed for the first time and healthy controls. Methods:Totally 80 MDD patients hospitalized from January 1, 2020 to March 30, 2021 and 80 healthy volunteers with normal physical examination in the same period were selected. Blood and fecal samples of patients with MDD and healthy controls were collected respectively. The indicators of serum glucose and lipid metabolism were detected by automatic biochemical analyzer, the concentrations of GLP-1 in plasma and feces were detected by ELISA, and the relative contents of Lactobacillus and Bifidobacterium in feces were detected by real-time PCR. The differences between two groups of glucose and lipid metabolism indicators, GLP-1 levels and the relative contents of Lactobacillus and Bifidobacterium in feces were analyzed. SPSS 22.0 software was used for statistical analysis. Independent sample t-test and analysis of variance were used for inter group comparison, and Pearson correlation analysis was used for correlation analysis. Results:Compared with the control group, the levels of serum TC, HDL, and LDL in the MDD group decreased ((3.99±0.85)mmol/L , (4.78±0.86)mmol/L; (1.18±0.29)mmol/L, (1.30±0.28)mmol/L; (2.64±0.70)mmol/L, (3.19±0.69)mmol/L; t=5.559, 2.371, 4.695, all P<0.05). The plasma and fecal GLP-1 levels of the MDD group were lower than those of the control group (plasma: (0.81±0.22)pmol/mL, (1.05±0.26)pmol/mL , t=4.509, P<0.01; feces: (2.23±0.46)pmol/mL , (2.47±0.37)pmol/mL, t=2.533, P<0.05). Compared with the control group, the relative contents of Lactobacillus(2.56±1.59, 3.51±2.21) and Bifidobacterium(2.24±1.89 , 3.17±2.08) in the MDD group decreased ( t=2.218, 2.082, both P<0.05). The level of plasma GLP-1 in the MDD group was negatively correlated with FPG, TG, and disease severity ( r=-0.281, -0.221, -0.437, P<0.05). The level of plasma GLP-1 in the control group was negatively correlated with FPG ( r=-0.580, P<0.01). The fecal GLP-1 level of the MDD group was negatively correlated with the severity of the disease ( r=-0.298, P<0.01), and the fecal GLP-1 level of the control group was positively correlated with fecal Lactobacillus and Bifidobacterium ( r=0.685, 0.428, P<0.01). Conclusion:MDD patients have abnormal glucose and lipid metabolism, decreased GLP-1 level and decreased relative content of intestinal Lactobacillus and Bifidobacterium. Changes in intestinal flora affect GLP-1 levels. GLP-1 can affect glucose and lipid metabolism and depressive symptoms in patients with MDD by binding to specific receptors in intestinal tract and central nervous system.
ABSTRACT
Objective:To investigate the significance of serum glycocholic acid (CG), total bile acid (TBA), and glucagon-like peptide-1 (GLP-1) in the transformation of fatty liver to liver cancer and their relationship with the body′s glucose and lipid metabolism.Methods:From May 2018 to August 2020, 96 patients with fatty liver (fatty liver group), 96 patients with liver cirrhosis (cirrhosis group) and 96 patients with liver cancer (liver cancer group) admitted to Jintang Hospital of West China Hospital of Sichuan University were selected. Ninety-six healthy physical examination patients were selected during the same period as the normal control group. Compared the general information, serum CG, TBA, GLP-1, glycosylated hemoglobin (HbA 1c), triacylglycerol (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) levels of each group. The correlation between serum CG, TBA, GLP-1 levels and the body′s glucose and lipid metabolism indicators were analyzed by Pearson correlation. The correlation between serum CG, TBA, GLP-1 and clinical stage were analyzed. Results:The levels of serum CG, TBA, GLP-1, and HbA 1c in the fatty liver group, cirrhosis group, liver cancer group were higher than those in the normal control group: (3.57 ± 1.06), (22.17 ± 8.44),(31.44 ± 9.65) mg/L vs. (1.26 ± 0.78) mg/L; (5.94 ± 1.26), (12.34 ± 4.02), (20.65 ± 5.17) μmol/L vs. (2.87 ± 0.59) μmol/L; (8.34 ± 1.55), (11.69 ± 3.26), (17.84 ± 2.78) pmol/L vs. (6.68 ± 1.24) pmol/L; (5.52 ± 0.31)%, (5.89 ± 0.27)%, (6.11 ± 0.23)% vs. (5.11 ± 0.36)%, and with the progression of the disease, the levels showed a rising trend, and the differences were statistically significant ( P<0.05). The levels of TG, TC, HDL-C, LDL-C in the cirrhosis group and liver cancer group were lower than those in the normal control group and fatty liver group, the differences were statistically significant ( P<0.05). The results of correlation analysis showed that serum CG, TBA, GLP-1 were positively correlated with HbA 1c ( P<0.05), and serum CG, TBA, GLP-1 were negatively correlated with TG, TC, HDL-C, and LDL-C ( P<0.05). With the increase of clinical stage, serum CG and TBA levels showed an increasing trend ( P<0.05). Conclusions:With the transformation of fatty liver to liver cancer, serum CG, TBA, and GLP-1 levels increase, and the change trend is closely related to the body′s glucose and lipid metabolism, which can provide a reference for the clinical improvement of fatty liver outcome evaluation mechanism.
ABSTRACT
ObjectiveTo evaluate the effects of high intensity interval training (HIIT) on patients with type 2 diabetes mellitus (T2DM). MethodsFrom May to October, 2021, twelve patients with T2DM were recruited with internet. An HIIT exercise intervention based on WHO Guidelines on Physical Activity and Sedentary Behaviour and World Health Organization Family of International Classifications (WHO-FICs) was constructed. They received aerobic combined with resistance training in a multi-combination HIIT using whole-body exercise, 30 to 35 minutes a time, three times a week, for eight weeks. Before and after intervention, their blood glucose levels, lipid levels, pancreatic fat content and body composition were measured. ResultsOne cased was dropped. After intervention, the fasting glucose, 2-hour postprandial glucose, hemoglobin A1c, fasting serum insulin, insulin resistance index, serum total cholesterol, serum triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, pancreatic fat content, body weight, body mass index, and body fat percentage improved (t > 2.258, P < 0.05). ConclusionHIIT exercise intervention based on the Guidelines and WHO-FICs could improve the related functions of patients with T2DM, such as blood glucose levels, blood lipid levels, pancreatic fat content and body composition, and reduce the consumption of hypoglycemic drugs.
ABSTRACT
Aim To study the effects of eugenol on hypoglycemic effect and hepatic glucose and lipid metabolism in type 2 diabetic mice, and to explore the possible mechanism. Methods The model of type 2 diabetes induced by long term high-fat diet was divided into four groups. The blood glucose and body weight of each group were measured once a week. After six weeks, the liver tissues of mice in each group were dissected and the liver mass and body mass of mice were weighed. Liver index, lipid metabolism and liver function were measured. Oral glucose tolerance test was performed. The levels of blood glucose, insulin, triglyceride, cholesterol, resistin, leptin, auxin, glucagon and plasminogen activator inhibitor-1 in serum were measured. He staining was used to observe the pathological changes of liver tissues. The expressions of SHP, pfoxo1, pCREB, PEPCK and G6Pase proteins in liver were detected by Western blot. Results Compared with HFD group, E40 group had lower body weight, smaller liver volume and healthy dark red. Compared with HFD group, E40 group decreased liver index, lipid metabolism and liver function. OGTT test showed that glucose tolerance was enhanced and the area under the curve was decreased in E40 group compared with HFD group. The levels of blood glucose, insulin, triglyceride, resistin, leptin, glucagon and plasminogen activator inhibitor-1 in E40 group were lower than those in HFD group. He staining showed that hepatocytes in HFD group were larger and accompanied with bullous steatosis than those in RD group. Hepatocyte steatosis and liver pathological state were significantly improved in E40 group. The results of Western blot showed that compared with HFD group, the expression of SHP, pfoxo1 and pCREB protein in E40 group was up-regulated, and the expression of PEPCK and G6Pase protein was down-regulated. Conclusions Eugenol can regulate the SHP/pFOXO1/PCREB/PEPCK/G6Pase signaling pathway, regulate glucose and lipid metabolism, inhibit insulin resistance, improve blood glucose level and glucose and lipid metabolism disorders in type 2 diabetes mellitus.
ABSTRACT
ObjectiveTo investigate the effect and mechanism of Mori Folium extract on the glucose and lipid metabolism disorders in the liver of rats with type 2 diabetes mellitus （T2DM） through the phosphatidylinositol 3-kinase/protein kinase B/peroxisome proliferation-activated receptor α/carnitine palmitoyl transferase-1 （PI3K/Akt/PPARα/CPT-1） signaling pathway. MethodThe T2DM model was induced by the high-fat diet combined with the intraperitoneal injection of streptozotocin （STZ）. The model rats were randomly divided into a model group， a metformin （0.2 g·kg-1） group， and a Mori Folium water extract （4.0 g·kg-1） group according to blood glucose and body weight. In the 8-week administration， fasting blood glucose was measured at the same time every week. The histomorphological and fat changes in the rat liver were observed by hematoxylin-eosin （HE） staining and oil red O staining. The levels of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） in the serum were measured by biochemical methods. Western blot （WB） was used to quantitatively detect the protein expression of p-PI3K，PI3K，p-Akt，Akt，PPARα，and CPT-1 in the rat liver. ResultAfter 8-week administration， the blood glucose of rats was higher in the model group than that in the control group （P<0.01）， and lower in the Mori Folium water extract group than that in the model group （P<0.01）. The results of HE staining showed that the liver tissue structure of the control group was complete， and the hepatocytes were arranged radially around the central vein， while the hepatocyte injury in the model group was obvious. Compared with the model group， the Mori Folium water extract group showed improved vacuolar degeneration and no lesions such as small bile duct hyperplasia. Oil red O staining showed that there was no obvious steatosis and necrosis in the hepatocytes of rats in the control group， and no lipid droplets in the hepatocytes were observed， while the model group showed increased lipid droplets. Mori Folium significantly reduced the lipid droplets in the liver. Biochemical analysis showed that the levels of TC， TG， LDL-C， AST， and ALT in the model group were significantly higher than those in control group （P<0.01）. The levels of TC， TG， LDL-C， AST， and ALT in the Mori Folium water extract group were significantly lower than those in the model group （P<0.05，P<0.01）. WB showed that the protein expression of p-PI3K/PI3K， p-Akt/Akt， PPARα， and CPT-1 in the model group were lower than those in the control group （P<0.01）. Mori Folium water extract could increase the protein expression of p-PI3K/PI3K， p-Akt/Akt， PPARα， and CPT-1 （P<0.05 or P<0.01）. ConclusionThe hypoglycemic mechanism of Mori Folium water extract may be related to the regulation of the PI3K/Akt/PPARα/CPT-1 signaling pathway.