Effect of modified citrus pectin on glycolysis of rabbit articular chondrocytes / 国际生物医学工程杂志

Objective:To investigate the effect of modified citrus pectin (MCP) on the glucose metabolism of rabbit articular chondrocytes.Methods:The third generation (P3) rabbit knee chondrocytes were extracted and cultured with 0 μg/ml (MCP0, control group) and 500 μg/ml of MCP (MCP500) for 3 days. Chondrocytes (P2-P7)were cultured continuously, and each generation of chondrocytes was treated with MCP0 and MCP500 medium for 3 days. Chondrocytes were treated with interleukin-1β (IL-1β) for 1 day and then treated with MCP0 and MCP500 medium for 3 days, respectively. Chondrocytes were treated with 2-deoxy-glucose (2DG) for 1 day and then treated with MCP0 and MCP500 medium for 3 days, respectively. After three days of culture, the proliferation of chondrocytes was calculated by CCK-8. Glucose uptake activity and lactate production of chondrocytes were measured by glucose and lactate detection kits. The synthesis of type Ⅱ collagen (COL2A1) in sequential chondrocytes was investigated by immunofluorescence staining. The gene expression of COL2A1, proteoglycan ( ACAN), SOX9, hypoxia-inducible factor-1α ( HIF-1α), glucose transporter-1 ( Glut-1), pyruvate kinase M2 ( PKM2), lactate dehydrogenase-A ( LDHA) and glucose transporter-1 ( Glut-3) were further detected by RT-qPCR. Results:Compared with the control group, MCP treatment could increase the glucose uptake activity and lactate production of chondrocytes, and enhance the gene expression ability of HIF-1α, Glut-1, PKM2 and ACAN. Besides, MCP treatment could stimulate chondrocyte proliferation, maintain chondrocyte phenotype, increase lactate production, and upregulate the expression of COL2A1, ACAN, SOX9, HIF-1α, Glut-1, PKM2 and LDHA. After the treatment with IL-1β, MCP treatment could increase glucose uptake activity and upregulate the expression of COL2A1, ACAN, HIF-1α and Glut-1. After treatment with 2DG, MCP treatment could increase glucose uptake activity and upregulate the expression of SOX9, HIF-1α, PKM2 and Glut-3 genes. Conclusions:MCP can enhance the glucose uptake capacity of chondrocytes and increase the level of chondrocyte glycolytic metabolism.

Effects of Bazhen Decoction combined with Baizhu Fuzi Decoction on glucose metabolism and estrogen levels in rats with polycystic ovary syndrome / 天津医药

Objective To study the regulation effects of Bazhen Decoction combined with Baizhu Fuzi Decoction on glucose metabolism and estrogen level in rats with polycystic ovary syndrome.Methods The rat model of polycystic ovary syndrome was established by subcutaneous injection of human chorionic gonadotropin(HCG)combined with insulin.Rats were randomly divided into the polycystic ovary syndrome group,the Baizhu Fuzi Tang group(6.4 g/kg),the Bazhen Tang group(9.2 g/kg),the Bazhen Tang combined with Baizhu Fuzi Tang group(11.55 g/kg)and the diethylstilbestrol group(0.5 mg/kg).A blank control group(unmodulated rats)was set up with 10 rats in each group.The uterine index of rats was determined and calculated.Fasting blood glucose(FBG),2 h postprandish blood glucose(2 h PBG)and fasting insulin(FINS)were determined and insulin sensitivity index(ISI)and insulin resistance index(IR)were calculated.Serum estradiol(E2),testosterone(T),luteinizing hormone(LH),follicle stimulating hormone(FSH),prolactin(PRL),anti-Mullerian tube hormone(AMH)and insulin-like growth factor 1(IGF-1),C-reactive protein(CRP),interleukin(IL)-6,tumor necrosis factor(TNF)-α,total peroxidase activity(T-AOC),superoxide dismutase(SOD)and malondialdehyde(MDA)levels in ovarian tissue were detected by enzyme-linked immunosorbent assay(ELISA).The pathological changes of ovarian tissue were detected by hematoxylin-eosin(HE)staining.Real-time quantitative polymerase chain reaction(qPCR)was used to determine mRNA levels of ARA70,CBP,SCR1 and HOXA10 in endometrium and mRNA expressions of AMPK,GLUT4 and PPARγ in ovarian tissue.Western blot assay was used to determine expression levels of AMPK,GLUT4 and PPARγ in ovarian tissue.Results Compared with the polycystic ovary syndrome group,uterine index,FINS,FBG,2 h PBG,IR levels,serum T,LH,FSH,PRL,AMH,IGF-1 levels,ovarian tissue CRP,IL-6,TNF-α,T-AOC and MDA level,endometrial ARA70,CBP,SCR1 mRNA level of rats decreased significantly in the Baizhu Fuzi decoction group,the Bazhen decoction group and the Bazhen decoction combined with Baizhu Fuzi decoction group(P＜0.05).ISI level,serum E2 level,ovarian tissue SOD level,endometrial HOXA10 mRNA level,ovarian tissue AMPK,GLUT4 and PPARγ mRNA and protein levels were significantly increased(P＜0.05).The above indexes were significantly changed in the Bazhen decoction and Bazhu Fuzi decoction group than those of the Bazhu Fuzi decoction group and the Bazhen decoction group(P＜0.05).Conclusion Bazhen Decoction combined with Baizhu Fuzi Decoction can regulate glucose metabolism,inhibit ovarian tissue oxidation and inflammatory damage,improve endometrium tolerance,regulate estrogen level,and improve the progression of polycystic ovary syndrome in rats.The mechanism may be related to the regulation of AMPK/GLUT4/PPARγ pathway.

Progress of the role of sclerostin in metabolic diseases / 中华内分泌代谢杂志

Lipid and glucose metabolism play crucial roles in maintaining energy homeostasis, and their dysregulation can lead to the development of metabolic disorders, such as obesity and diabetes. Studies indicate that the skeleton, involved in lipid and glucose metabolism, functions as an endocrine organ, regulating systemic metabolism through bone-derived molecules. Sclerostin is a protein mainly produced by osteocytes, possessing the ability to inhibit bone formation, and its antibodies have become therapeutic targets for treating osteoporosis. Recent evidence suggests that sclerostin also plays a role in lipid and glucose metabolism disorders. Therefore, through summarizing in vitro and in vivo researches, this article reviews the role of sclerostin in lipid and glucose metabolism, its relationship with obesity and diabetes, and potential role in the treatment of metabolic diseases in the future.

Metabolic reconfiguration in vitiligo: progress and future / 中华皮肤科杂志

Based on the results of the latest basic research on vitiligo, this article elucidates the significance of reconfiguration of glucose metabolism, lipid metabolism, amino acid metabolism, and metabolism of gut microbiota in the pathogenesis of vitiligo, attempts to delineate a panoramic picture of metabolic reconfiguration in vitiligo, and discusses the importance of dialectically and uniformly grasping the crosstalk between multiple metabolic pathways, and of thinking about the mechanisms of action of multiple metabolic pathway reconfiguration in the occurrence of vitiligo in individuals from a holistic perspective in future basic studies, in order to promote the understanding of the vitiligo pathogenesis and explore potential treatment methods for vitiligo.

Modern Thinking on the Indications of Daoyin （导引） based on the Theory of "Wei （痿） Diseases should be Treated by Daoyin" / 中医杂志

It has been proposed by Basic Questions On Proper Therapies for Different Diseases Geographically （《素问·异法方宜论篇》） that "wei （痿） diseases should be treated by Daoyin （导引）". Furthermore， it is clarified that the indications of Daoyin are those conditions related to spleen and dampness caused by dampness pathogen， excessive food intake and less exercise， and mainly manifested as heavy limbs， fatigue and flaccidity， which is similar to the metabolic imbalance in the early stage of glucose or lipid metabolism disorder in modern medicine. Based on modern clinical and basic research evidence， Daoyin can inhibit the response of inflammation， alleviate oxidative stress， regulate intestinal microbiota， and modulate gene expression to improve metabolic abnormalities， and this will provide ideas for researches on the indications of Daoyin.

The Correlation between Traditional Chinese Medicine Constitution and the Progression of Abnormal Glucose Metabolism in Community Population： A Case-control Study / 中医杂志

ObjectiveTo investigate the role of traditional Chinese medicine （TCM） constitution in the progression of abnormal glucose metabolism among community population. MethodsA total of 393 community residents who participated in community diabetes screening from 2019 to 2021 and had complete physical examination data at baseline and at the 2nd year follow-up were selected. According to the results of glucose tolerance tests， community residents were divided into the abnormal glucose metabolism progression group and non-progression group， and were matched at the ratio of 1∶2 using the propensity score matching. The influencing factors related to diabetes at baseline were collected for both groups. The traditional Chinese medicine constitution was determined among population in two groups. The differences of influencing factors and traditional Chinese medicine constitution between the two groups were compared. Logistic regression analysis was used to analyze the risk factors for the progression of abnormal glucose metabolism. ResultsFinally， 131 patients were included in the progression group and 262 patients in the non-progression group. Compared to the non-progression group， the progression group had significantly higher proportion of hyperlipidemia history ， hyperglycemia history， phlegm-dampness constitution， and blood stasis constitution （P＜0.05 or P＜0.01）. Univariate logistic regression analysis revealed that the history of hyperlipidemia （P=0.011）， history of hyperglycemia （P＜0.001）， the family history of diabetes （P＜0.001）， yin-deficiency constitution （P=0.047）， phlegm-dampness constitution （P=0.011） and blood-stasis constitution （P=0.008） were risk factors for the progression of abnormal glucose metabolism. Multivariate logistic regression analysis indicated that the history of hyperglycemia （P＜0.001）， yin-deficiency constitution （P=0.026） and blood-stasis constitution （P=0.032） were independent risk factors for the progression of abnormal glucose metabolism. ConclusionThe history of hyperglycemia， yin-deficiency constitution and blood-stasis constitution may be the risk factors for the progression of abnormal glucose metabolism.

Intervention effect and mechanism of Wuwei baogan pill on mice with non-alcoholic fatty liver disease / 中国药房

OBJECTIVE To investigate the intervention effect and mechanism of Wuwei baogan pill on mice with non- alcoholic fatty liver disease （NAFLD）. METHODS The mice were given high-fat and high-sugar diet for 19 weeks to induce NAFLD model. The model mice were randomly grouped into model group， positive control group （polyene phosphatidylcholine capsules， 23.30 mg/kg）， Wuwei baogan pill low-dose， medium-dose and high-dose groups （0.11， 0.23， 0.45 g/kg）， with 8 mice in each group； the normal group was additionally set up without modeling. Administration groups were given relevant medicine intragastrically， and model group and normal group were given constant volume of normal saline， once a day， for consecutive 4 weeks. After the last administration， glucose metabolism （including fasting blood glucose， fasting insulin， insulin resistance index）， liver function [liver index， alanine aminotransferase （ALT）， aspartate aminotransferase （AST），liver tissue pathological score]， lipid metabolism [triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， and high- density lipoprotein cholesterol （HDL-C）] were measured； the pathological morphology of liver tissue， as well as fibrosis， lipid droplet formation， and glycogen synthesis were observed； the levels of free fatty acid （FFA） in serum and inflammatory factors in liver tissue [tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β] were detected； the expressions of insulin receptor substrate/phosphoinositide 3-kinase/protein kinase B/ glycogen synthase kinase 3β （IRS/PI3K/AKT/GSK3β） signaling pathway-related protein in liver tissue were investigated. RESULTS After intervention with high-dose Wuwei baogan pill， liver index of NAFLD mice， serum levels of ALT， AST， FFA， TC， TG and LDL-C， the levels of TNF-α， IL-6 and IL-1β in liver tissue， fasting blood glucose， fasting insulin， insulin resistance index， liver tissue pathological score， proportions of fibrotic staining area and lipid droplet staining area all significantly decreased （P＜0.05）； the level of HDL-C， proportion of glycogen staining area， the phosphorylation of IRS1， PI3K， AKT and GSK3β protein increased significantly （P＜0.05）； the degree of liver cell necrosis and steatosis was reduced， and the fibrotic lesions were alleviated. The above indexes of mice were improved in Wuwei baogan pill low-dose and medium-dose groups， but there was no statistically significant difference in some indexes. CONCLUSIONS Wuwei baogan pill can regulate lipid and glucose metabolism disorders in the liver of NAFLD mice， and improve liver injury， the mechanism of which may be associated with the activation of IRS/PI3K/AKT/GSK3β signaling pathway.

Intervention effect and mechanism of Wuwei baogan pill on mice with non-alcoholic fatty liver disease / 中国药房

OBJECTIVE To investigate the intervention effect and mechanism of Wuwei baogan pill on mice with non- alcoholic fatty liver disease （NAFLD）. METHODS The mice were given high-fat and high-sugar diet for 19 weeks to induce NAFLD model. The model mice were randomly grouped into model group， positive control group （polyene phosphatidylcholine capsules， 23.30 mg/kg）， Wuwei baogan pill low-dose， medium-dose and high-dose groups （0.11， 0.23， 0.45 g/kg）， with 8 mice in each group； the normal group was additionally set up without modeling. Administration groups were given relevant medicine intragastrically， and model group and normal group were given constant volume of normal saline， once a day， for consecutive 4 weeks. After the last administration， glucose metabolism （including fasting blood glucose， fasting insulin， insulin resistance index）， liver function [liver index， alanine aminotransferase （ALT）， aspartate aminotransferase （AST），liver tissue pathological score]， lipid metabolism [triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， and high- density lipoprotein cholesterol （HDL-C）] were measured； the pathological morphology of liver tissue， as well as fibrosis， lipid droplet formation， and glycogen synthesis were observed； the levels of free fatty acid （FFA） in serum and inflammatory factors in liver tissue [tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β] were detected； the expressions of insulin receptor substrate/phosphoinositide 3-kinase/protein kinase B/ glycogen synthase kinase 3β （IRS/PI3K/AKT/GSK3β） signaling pathway-related protein in liver tissue were investigated. RESULTS After intervention with high-dose Wuwei baogan pill， liver index of NAFLD mice， serum levels of ALT， AST， FFA， TC， TG and LDL-C， the levels of TNF-α， IL-6 and IL-1β in liver tissue， fasting blood glucose， fasting insulin， insulin resistance index， liver tissue pathological score， proportions of fibrotic staining area and lipid droplet staining area all significantly decreased （P＜0.05）； the level of HDL-C， proportion of glycogen staining area， the phosphorylation of IRS1， PI3K， AKT and GSK3β protein increased significantly （P＜0.05）； the degree of liver cell necrosis and steatosis was reduced， and the fibrotic lesions were alleviated. The above indexes of mice were improved in Wuwei baogan pill low-dose and medium-dose groups， but there was no statistically significant difference in some indexes. CONCLUSIONS Wuwei baogan pill can regulate lipid and glucose metabolism disorders in the liver of NAFLD mice， and improve liver injury， the mechanism of which may be associated with the activation of IRS/PI3K/AKT/GSK3β signaling pathway.

BMSC-Exo alleviates depression-like behaviors in mice by inducing hippocampal energy metabolism and microangiogenesis / 中华神经医学杂志

Objective:To investigate the effect of bone mesenchymal stem cells derived exosomes (BMSC-Exo) on improving hippocampal microangiogenesis, energy metabolism, and behaviors in depression mouse models.Methods:(1) Mouse bone marrow mesenchymal stem cells were isolated and cultured to extract BMSC-Exo; BMSC-Exo morphology was observed by transmission electron microscopy, BMSC-Exo particle diameter ranges were determined by Zetaview analyzer, and expressions of CD9 and CD63 in BMSC-Exo were detected by Western blotting. (2) Depression models were established in 2 mice by chronic unforeseeable mild stress (CUMS); 24 h after stereotaxic injection of phosphate buffer solution (PBS) or DiR labeled BMSC-Exo, BMSC-Exo uptake was detected by in vivo imaging system. (3) Thirty-six mice were randomly divided into control group, model group and BMSC-Exo group ( n=12); CUMS was used to establish depression models in the latter 2 groups; brain stereotaxic injection of 1 μL BMSC-Exo was given to mice in the BMSC-Exo group after modeling, and same amount of PBS was given to the control group; behaviors were observed by forced swimming test (FST), tail suspension test (TST) and open field test (OFT); hippocampal microvascular length and number were detected by alkaline phosphatase staining; energy metabolism in the hippocampus was detected by micro positron emission tomography/computed tomography (mPET/CT); glucose transporter 1 (GLUT1) expression in the hippocampus was detected by Western blotting. Results:(1) BMSC-Exo had a typical disk-like vesicle-like structure with particle size of (100.5±1.4) nm; Western blotting confirmed that CD9 and CD63 expressed in BMSC-Exo. (2) In vivo imaging showed no fluorescence in the brain and liver after PBS injection, but obvious local fluorescence after BMSC-Exo injection. (3) Compared with the control group, the model group and BMSC-Exo group had significantly longer rest time in FST and TST and shorter movement distance and time in the central region of OFT ( P<0.05); compared with the model group, BMSC-Exo group had significantly shorter rest time in FST and TST and longer movement distance and time in the central region of OFT ( P<0.05). Compared with the control group, the model group and BMSC-Exo group had significantly decreased standard uptake value (SUV) of regions of interest, microvascular length and number, and GLUT1 expression in the hippocampus ( P<0.05); compared with the model group, the BMSC-Exo group had significantly higher SUV, microvascular length and number, and GLUT1 expression in the hippocampus ( P<0.05). Positive correlations were noted between hippocampal microvascular length and SUV and between microvascular number and SUV in the 3 groups ( r=0.540, P<0.001; r=0.600, P<0.001). Conclusion:BMSC-Exo could promote microangiogenesis energy metabolism in the hippocampus to improve depression-like behaviors in depression mouse models.

The combination of berberine and cinnamon polyphenol can improve glucose metabolism in T2DM rats through Bas-TGR5-GLP-1 / 药学学报

Berberine (BBR) is the main pharmacological active ingredient of Coptidis, which has hypoglycemic effect, but its clinical application is limited due to its poor oral bioavailability. Polyphenols, derived from cinnamon, are beneficial for type 2 diabetes mellitus (T2DM). The combination of both may have an additive effect. The aim of this study was to investigate the hypoglycemic effect and mechanism of combined medication in diabetic rats. The modeling rats were randomly divided into 5 groups (berberine group, cinnamon group, combined group, metformin group, diabetic control group) and normal control group. The animal experiments were approved by the Animal Ethics Committee (approval number: HMUIRB2022003). The subjects were given orally, and the control group was given equal volume solvent and body weight was measured weekly. Thirty days after administration, oral glucose tolerance test and insulin sensitivity test were performed, and fasting blood glucose (FBG), glycated serum protein (GSP), and serum insulin (INS) levels were detected; high-throughput sequencing technology was used to detect intestinal microbiota structure; real-time quantitative PCR (RT-qPCR) and Western blot were used to detect G protein-coupled receptor 5 (TGR5) and glucagon-like peptide-1 (GLP-1) expression levels. The results showed that, compared with the diabetic control group, the levels of FBG (P < 0.01) and GSP (P < 0.01) in the combined group were lower, and the insulin resistance was improved, which was better than that in the berberine group. Combined treatment increased the relative abundance of Bacteroides, Prevotella and Lactobacillus, reversed the decrease in Lactobacillus in the berberine alone induction group, and the combination of the two could promote the expression of TGR5 and GLP-1. In summary, the combined application of cinnamon and berberine can regulate glucose metabolism better than the application of berberine alone. Berberine combined with cinnamon can improve the function of pancreatic islet β cells in diabetes mellitus type 2 rats by changing the intestinal microbiota, increasing the expression of TGR5 and GLP-1 proteins, and thereby better regulating glucose metabolism.

Effect of Precocious Puberty on Glucose and Lipid Metabolism in Female Rats / 中山大学学报(医学科学版)

ObjectiveTo explore the effect of precocious puberty on glucose metabolism and lipid metabolism in female rats. MethodsSixty two-day-old female rats were randomly divided into 2 groups. When aged 5 days， the precocious puberty group and normal group were given a single subcutaneous injection of danazol and solvent soybean oil respectively. The vaginal opening of rats was monitored from their 21 days of age. After 12 hours of fasting， all successful modeling rats were randomly executed within 3 days after vaginal opening， when aged 7 and 12 weeks. Then we measured the rats’ body weight and length， determined the concentrations of glucose， insulin， blood lipids， estradiol， leptin and adiponectin with enzyme-linked immunosorbent assay and observed the pathological changes of perirenal fat， uterus and ovary. ResultsFor body weight and length， rats in the precocious puberty group were smaller than those in the normal group within 3 days after vaginal opening， but which did not affect their subsequent growth and development， and there was no significant difference between the two groups at 7 and 12 weeks of age. Within 3 days after vaginal opening， insulin levels had significant difference between the two groups （P = 0.001）， the precocious group showed hyperinsulinemia and increased number of perirenal adipocytes. At three execution times， no significant difference was noted in estradiol， leptin and adiponectin levels between the two groups. The same was true in the ratios of ovary or uterus to body weight between the two groups. ConclusionsPrecocious puberty makes earlier onset of pubertal development and allows body maladaptation to the sudden changes of the internal environment. However， the changes due to precocious puberty are temporary and reversible， and they may become normal in adulthood.

The role of glucose metabolism reprogramming and its targeted therapeutic agents in inflammation-related diseases / 药学学报

Cells undergo glucose metabolism reprogramming under the influence of the inflammatory microenvironment, changing their primary mode of energy supply from oxidative phosphorylation to aerobic glycolysis. This process is involved in all stages of inflammation-related diseases development. Glucose metabolism reprogramming not only changes the metabolic pattern of individual cells, but also disrupts the metabolic homeostasis of the body microenvironment, which further promotes aerobic glycolysis and provides favourable conditions for the malignant progression of inflammation-related diseases. The metabolic enzymes, transporter proteins, and metabolites of aerobic glycolysis are all key signalling molecules, and drugs can inhibit aerobic glycolysis by targeting these specific key molecules to exert therapeutic effects. This paper reviews the impact of glucose metabolism reprogramming on the development of inflammation-related diseases such as inflammation-related tumours, rheumatoid arthritis and Alzheimer's disease, and the therapeutic effects of drugs targeting glucose metabolism reprogramming on these diseases.

Retrospective cohort analysis of the relationship between correcting abnormal glucose metabolism and controlling the risk of death of digestive system malignant tumors / 公共卫生与预防医学

Objective To investigate the relationship between correcting abnormal glucose metabolism and mortality risk of malignant tumors of digestive system. Methods A retrospective cohort study was conducted. 1308 patients with abnormal glucose metabolism in our hospital from January 2019 were divided into exposed group (n=777) and non-exposed group (n=531) according to the presence or absence of glucose metabolism correction therapy. The patients were retrospectively followed up until December 2022. The incidence of digestive system tumors and the influencing factors of tumors were compared between the two groups. Results There were 31 patients with digestive system tumor and 9 patients died. The incidence of digestive system tumors was lower in the exposed group (3/777) than in the non-exposed group (28/531). The mortality rate in the exposed group (1/777) was lower than that in the non-exposed group (8/531). Cox regression model analysis showed that correcting abnormal glucose metabolism was a protective factor for the risk of death from malignant tumors of the digestive system in patients (HR value1, P<0.05). Conclusion Correcting abnormal glucose metabolism is of positive significance in reducing the risk of death from malignant tumors of digestive system. Patients with increased FBG, abnormal lipid metabolism, increased pulse pressure difference, family history of malignant tumors and alcohol consumption should pay special attention to correct abnormal glucose metabolism in time.

Effects of an antioxidants cocktail on glucose metabolism at rest, during exercise, and during a glucose load in healthy young subjects

Background: Reactive oxygen species (ROS) regulate glucose metabolism (GM) in skeletal muscle by improving the translocation of GLUT4. Antioxidant supplementation could block this physiological effect, altering glucose signaling during exercise. However, there is limited evidence in humans on whether antioxidant intake affects GM. Therefore, we aimed to determine the effect of an antioxidant cocktail (AOC) on GM at rest and during metabolic challenges. Methods: Ten healthy male subjects received AOC supplementation (1000 mg of Vitamin C, 600 IU of Vitamin E, and 600 mg of α-lipoic acid) or placebo (2.000 mg of talc) before two trials conducted 7 days apart. Trial 1: AOC 120 and 90 minutes before an endurance exercise (EEX) bout at 60 % of maximal oxygen uptake (VO2max); Trial 2: AOC 120 and 90 minutes before an oral glucose tolerance test (OGTT; 75 g glucose). Measurements of gas exchange and capillary blood samples were collected every 15 minutes during both trials. Results: AOC supplementation increased resting glucose levels (p<0.05). During Trial 1 (EEX), the AOC increased carbohydrate oxidation (CHOox) (p= 0.03), without effect in glucose blood levels. During Trial 2 (OGTT), the AOC supplementation had no significant effect on GM parameters. Conclusion: Acute supplementation with AOC increased resting glucose levels and CHOox during EEX in healthy subjects, with no effect on GM during the OGTT.

Antecedentes: Las especies reactivas de oxígeno (ROS) regulan el metabolismo de la glucosa (GM) en el músculo esquelético al mejorar la translocación de GLUT4. La suplementación con antioxidantes podría bloquear este efecto fisiológico, alterando la señalización de la glucosa durante el ejercicio. Sin embargo, existe evidencia limitada en humanos sobre si la ingesta de antioxidantes afecta el GM. Por lo tanto, nuestro objetivo fue determinar el efecto de un cóctel de antioxidantes (AOC) en el GM en reposo y durante desafíos metabólicos. Métodos: Sujetos sanos (sexo masculino; n= 10) recibieron suplementos de AOC (1.000 mg de vitamina C, 600 UI de vitamina E y 600 mg de ácido α-lipoico) o placebo (2.000 mg de talco) previo a dos pruebas realizadas con 7 días de diferencia. Prueba 1: AOC 120 y 90 minutos antes de una serie de ejercicio de resistencia (EEX) al 60% del consumo máximo de oxígeno (VO2max); prueba 2: AOC 120 y 90 minutos antes de una prueba de tolerancia oral a la glucosa (OGTT; 75 g de glucosa). Se obtuvieron datos de intercambio de gaseoso y muestras de sangre capilar cada 15 minutos durante ambas pruebas. Resultados: la suplementación con AOC aumentó los niveles de glucosa en reposo (p<0,05). Durante la prueba 1 (EEX), el AOC aumentó la oxidación de carbohidratos (CHOox) (p= 0,03), sin efecto en los niveles de glucosa en sangre. Durante la prueba 2 (OGTT), la suplementación con AOC no tuvo un efecto significativo en los parámetros de GM. Conclusión: Una suplementación aguda con AOC aumentó los niveles de glucosa en reposo y la CHOox durante EEX en sujetos sanos, sin efecto sobre el GM durante la OGTT.

El ayuno intermitente y sus efectos en la salud metabólica en humanos / Intermittent fasting and human metabolic health

Intermittent fasting (IF) has gained increasing scientific and general attention. Most studied forms of IF include alternate-day fasting, modified alternate-day fasting, and time-restricted eating (TRE). Several cardiometabolic effects of IF have been described in animal models and, to a lesser extent, in humans. This review analyzes the impact of IF on weight loss, glucose metabolism, blood pressure, and lipid profile in humans. A literature search was conducted in the Pubmed/Medline, Scopus, and Google Scholar databases. Controlled observational or interventional studies in humans, published between January 2000 and June 2021, were included. Studies comparing IF versus religious fasting were not included. Most studies indicate that the different types of IF have significant benefits on body composition, inducing weight loss and reducing fat mass. Changes in cardiometabolic parameters show more divergent results. In general, a decrease in fasting glucose and insulin levels is observed, together with an improved lipid profile associated with cardiovascular risk. High heterogeneity in study designs was observed, particularly in studies with TRE, small sample sizes, and short-term interventions. Current evidence shows that IF confers a range of cardiometabolic benefits in humans. Weight loss, improvement of glucose homeostasis and lipid profile, are observed in the three types of IF protocols evaluated.

Baicalin inhibits PDK1 to mediate glucose metabolism reprogramming and intervene rheumatoid arthritis synovial inflammation / 药学学报

This study started from the effect of baicalin (BC), the main active component of the labiaceae plant Scutellaria baicalensis, on collagen-induced arthritis (CIA) in rats, to explore the mechanism of glucose metabolism reprogramming in fibroblast like synoviocytes (FLSs), a key effector cell of synovial inflammation in rheumatoid arthritis (RA). First of all, CIA rats and tumor necrosis factor-α (TNF-α)-induced RASFs in vitro and in vivo models were established, the arthritis index (AI) score and histopathological changes of CIA rats after BC administration were observed, and the levels of inflammatory factors in serum and cell supernatant were quantified by ELISA, immunocytochemistry and Western blot were used to detect the expression of G-protein-coupled receptor 81 (GPR81) and pyruvate dehydrogenase kinase 1 (PDK1) proteins. In addition, the kit was used to measure the levels of key products and enzyme activities in glucose metabolism reprogramming. The results showed that BC (50, 100 and 200 mg·kg-1) could alleviate the symptoms of arthritis in CIA rats in a dose-dependent manner, inhibit synovial hyperplasia, alleviate the infiltration of inflammatory cells, down-regulate the levels of pro-inflammatory factors TNF-α and interleukin (IL)-1β, and up-regulate the levels of anti-inflammatory factor IL-10 in CIA rats. At the same time, the secretion levels of lactate, pyruvate, acetyl-CoA, citrate and the activity of lactate dehydrogenase B (LDH-B) were decreased, and the expressions of GRP81 and PDK1 were down-regulated, suggesting that BC mediated the reprogramming process of glucose metabolism. However, when GPR81 inhibitor 3-OBA inhibited lactate uptake, the activity of LDH-B was significantly increased, suggesting that BC inhibited the expression of PDK1, a key enzyme in the reprogramming metabolism from glycolysis to oxidative phosphorylation. All animal experiments in this study were conducted in accordance with the ethical standards of the Laboratory Animal Care Center of Anhui University of Chinese Medicine (approval number: AHUCM-rats-2021049). These studies revealed that baicalin mediated metabolic reprogramming of RASFs from glycolysis to oxidative phosphorylation by inhibiting PDK1 protein expression, and alleviated joint inflammation in CIA rats.

Pathogenesis of Metabolic Remodeling of Energy Substrate Based on Theory of Deficient Qi Stagnation and Progress of Chinese Medicine Intervention / 中国实验方剂学杂志

In the case of cardiac dysfunction， energy metabolism changes and the metabolism of myocardial substrates is reconstructed， as manifested by variation in the selection and utilization of energy substrates such as fatty acids and glucose. Persistent metabolic disorders of substrates will decrease energy supply， thus resulting in the occurrence and development of heart failure. Metabolic remodeling of substrate is resulted from the decline of visceral function and the accumulation of pathological products. Deficient Qi stagnation is the core pathogenesis. Deficient Qi （heart Qi deficiency， insufficient energy） is the root cause， which exists in the whole disease course. Stagnation （phlegm， blood stasis， fluid， lipid toxic products， lactic acid， etc.） is the symptom， which evidences the aggravation of the disease. Deficient Qi and stagnation are intertwined and causal， which form a spiral vicious circle. The typical syndrome is excess resulted from deficiency and deficiency-excess in complexity. The treatment principle is reinforcing healthy Qi and tonifying deficiency， dredging and removing pathogen. At the early stage， the method of reinforcing healthy Qi and tonifying deficiency （benefiting Qi） should be used， and the method of dredging and removing pathogen （activating blood） can be applied according to the conditions of patients. At the middle and late stages， both reinforcing healthy Qi and tonifying deficiency （benefiting Qi and warming Yang） and dredging and removing pathogen （activating blood， resolving stasis， and excreting water） should be emphasized. Chinese medicine can be applied according to the pathogenesis， thereby promoting the utilization of fatty acids， glucose， and other substrates and reducing the accumulation of toxic products derived from metabolic remodeling of substrate. Thus， both the root cause and symptoms can be alleviated， further improving cardiac energy metabolism and heart function.

Expression of Key Enzymes in Glucose Metabolism in Chronic Mountain Sickness and Its Correlation with Phenotype / 中国实验血液学杂志

OBJECTIVE@#To explore the pathogenesis of erythrocytosis by detecting the key enzymes of glucose metabolism and glucose transporter in bone marrow erythrocytes of chronic mountain sickness (CMS), and analyzing its correlation with hemoglobin.@*METHODS@#Twenty CMS patients hospitalized in Qinghai Provincial People's Hospital from January 2019 to December 2020 were selected as CMS group. Twenty males with leukocyte count > 3.5×109/L who had accepted bone marrow aspiration and had normal result were taken as control group. The mRNA and protein expression of key enzymes and glucose transporter in glucose metabolism in bone marrow CD71+ erythrocytes were detected by real time qPCR and Western blot, respectively. Glucose, lactic acid and 2,3-diphosphoglycerate in the bone marrow supernatant and serum were tested by ELISA. The mRNA and protein expression of key enzymes and glucose transporter, glucose, lactic acid and 2,3-diphosphoglycerate of the two groups were compared. Pearson correlation was used to analyze the correlation between key enzymes, glucose transporter in glucose metabolism in bone marrow CD71+ erythrocytes and hemoglobin.@*RESULTS@#The expression of HK2, GLUT1 and GLUT2 mRNA in the CMS group were higher than those in the control group (P<0.001), while the expression of HK1, OGDH and COX5B mRNA were not different. The expression of HK2, GLUT1 and GLUT2 protein in the CMS group were higher than those in the control group (P<0.05). The levels of glucose and lactic acid in the bone marrow supernatant and serum in the CMS group were not different from those in the control group, while the level of 2,3-diphosphoglycerate was higher (P<0.001). Both HK2 and GLUT2 proteins were positively correlated with hemoglobin (r=0.511, 0.717).@*CONCLUSION@#CMS patients may increase glycolysis by increasing the expression of HK2, and promote the utilization of glucose through high expression of GLUT1 and GLUT2 to meet the need of energy supply.

AAZ2 induces mitochondrial-dependent apoptosis by targeting PDK1 in gastric cancer / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Drastic surges in intracellular reactive oxygen species (ROS) induce cell apoptosis, while most chemotherapy drugs lead to the accumulation of ROS. Here, we constructed an organic compound, arsenical N-‍(4-(1,3,2-dithiarsinan-2-yl)phenyl)acrylamide (AAZ2), which could prompt the ROS to trigger mitochondrial-dependent apoptosis in gastric cancer (GC). Mechanistically, by targeting pyruvate dehydrogenase kinase 1 (PDK1), AAZ2 caused metabolism alteration and the imbalance of redox homeostasis, followed by the inhibition of phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway and leading to the activation of B-cell lymphoma 2 (Bcl2)/Bcl2-associated X (Bax)/caspase-9 (Cas9)/Cas3 cascades. Importantly, our in vivo data demonstrated that AAZ2 could inhibit the growth of GC xenograft. Overall, our data suggested that AAZ2 could contribute to metabolic abnormalities, leading to mitochondrial-dependent apoptosis by targeting PDK1 in GC.

Research Progress on Correlation of Glucose Metabolism Mechanism with Invasion and Metastasis of Nasopharyngeal Carcinoma Cells / 肿瘤防治研究

Metastasis is the main cause of cancer-related death. Growing evidence has shown that changes in glucose metabolism in nasopharyngeal carcinoma cells affect the invasion and metastasis of nasopharyngeal carcinoma through many pathways. This review summarizes the molecular mechanism underlying abnormal glucose metabolism in nasopharyngeal carcinoma cells and analyzes its relationship with the invasion and metastasis of nasopharyngeal carcinoma, including aerobic glycolysis, aerobic oxidation, and pentose phosphate pathway. The aim is to provide novel approaches using the relationships among glucose metabolism, invasion, and metastasis in the targeted therapy of nasopharyngeal carcinoma.