Effects of electroacupuncture on the glucose-lipid metabolism and the expression of ZAG and GLUT4 in the femoral quadriceps and adipose tissue in the rats with type 2 diabetes mellitus / 中国针灸

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.

Expression and Function of Zinc-α2-Glycoprotein / 神经科学通报·英文版

Zinc-α2-glycoprotein (ZAG), encoded by the AZGP1 gene, is a major histocompatibility complex I molecule and a lipid-mobilizing factor. ZAG has been demonstrated to promote lipid metabolism and glucose utilization, and to regulate insulin sensitivity. Apart from adipose tissue, skeletal muscle, liver, and kidney, ZAG also occurs in brain tissue, but its distribution in brain is debatable. Only a few studies have investigated ZAG in the brain. It has been found in the brains of patients with Krabbe disease and epilepsy, and in the cerebrospinal fluid of patients with Alzheimer disease, frontotemporal lobe dementia, and amyotrophic lateral sclerosis. Both ZAG protein and AZGP1 mRNA are decreased in epilepsy patients and animal models, while overexpression of ZAG suppresses seizure and epileptic discharges in animal models of epilepsy, but knowledge of the specific mechanism of ZAG in epilepsy is limited. In this review, we summarize the known roles and molecular mechanisms of ZAG in lipid metabolism and glucose metabolism, and in the regulation of insulin sensitivity, and discuss the possible mechanisms by which it suppresses epilepsy.

Correlation between plasma zine-α2-glycoprotein and degree of coronary atherosclerosis lesion / 重庆医学

Objective To observe the correlation between zinc-a2-glycoprotein (ZAG) in human plasma and the degree of coronary atherosclerosis lesion.Methods A total of 242 research subjects were included.The clinical indexes were perfected and plasma ZAG level was detected.The coronary angiography was performed.The subjects were divided into the coronary atherosclerosis group (CAD group) and control group according to the examination results.The Gensini score was used to assess the degree of coronary artery lesion,different degree subgroups were divided according to the assessment results.The correlation between the ZAG level with the clinical indexes was analyzed by Spearman analysis.The ROC curve was used to evaluate the efficiency of ZAG in the diagnosis of coronary atherosclerosis and its sensitivity and specificity were analyzed.Results The plasma ZAG level in the CAD group was significantly lower than that in control group,the difference was statistically significant [(45.12±5.02)μg/mL vs.(53.93±2.96)μg/mL,P＜0.01].With the increase of Gensini score,plasma ZAG level showed the decreasing trend,the difference among the groups were statistically significant (P＜0.05).The Spearman correlation analysis showed that body mass index (BMI),waist circumference and waist to hip ratio(WHR) were negatively correlated with ZAG (P＜0.05),and positively correlated with high density lipoprotein cholesterol(HDL-C,P＜0.05).The sensitivity of plasma ZAG for evaluating coronary atherosclerosis was 89.8％ and its specificity was 91.2％.Conclusion Plasma ZAG is negatively correlated with the severity of coronary atherosclerosis lesion,and its level detection has a certain value in the screening of coronary atherosclerosis.

Change of serum zinc-α2-glycoprotein level before and after methimazol treatment in hyperthyroidism patients with Graves disease / 重庆医学

Objective To explore the roles and possible significance of zinc-α2-glycoprotein(ZAG) in Graves disease(GD) by detecting the change of serum ZAG level before and after methimazol(MMI) treatment in the patients with initial onset of Graves disease.Methods The enzyme linked immunosorbent assay(ELISA) was adopted to detect serum ZAG level in healthy population,patients with newly diagnosed GD and GD patients treated by 12-week MMI treatment.The serum thyroid hormones and thyroid related autoantibodies were determined by adopting the electrochemiluminescence immunoassay.The blood lipid levels were examined by enzymatic colorimetry.Furthermore the relationship between serum ZAG level with thyroid function,thyroid related autoantibodies and blood lipid in the patients with initial onset of GD was analyzed.Results The levels of ZAG,FT3,FT4,TT3,TT4,TGAb,TPO and TRAb in the patients with newly diagnosed GD were much higher than those in the age-and gender-matched normal healthy population,while the TSH level was significantly lower than that in the normal control group(P＜0.05);after 12-week MMI treatment in the patients with initial onset of GD,the levels of serum ZAG,FT3,FT4,TT3,TT4 and TRAb were markedly decreased,whereas the TSH level was significantly enhanced(P＜0.05 or P＜0.01).The correlation study showed that fasting serum ZAG level in the GD patients was positively correlated with FT3,FT4,TT3 and TT4(P＜0.05);and negatively correlated with TSH,FFA,TC and TG(P＜0.05).With fasting serum ZAG in the GD patients as the dependent variable,the multiple linear regression analysis showed that TSH,TC and TG were the independent related factors of plasma ZAG level.Conclnsion The serum ZAG level is closely correlated with the occurrence and development of GD,and might play an important role in the blood lipids metabolism of GD patients.

Correlation between zinc-α2-glycoprotein and hyperuricemia / 医学研究生学报

Objective Few reports are seen about the relationship of zinc-α2-glycoprotein ( ZAG ) with hyperuricemia ( HUA) . This study aimed to explore the correlation between ZAG and HUA by detecting the mRNA and protein expressions of ZAG in patients with HUA and in healthy subjects with normal uric acid ( NUA) . Methods We enrolled 74 HUA patients and another 74 NUA subjects in this study. We collected blood samples for determination of the mRNA and protein expressions of serum ZAG by real-time PCR and ELISA respectively, followed analysis of the differences in the expressions of ZAG mRNA and protein between the two groups. Results Compared with the NUA subjects, the HUA patients showed significantly increased expressions of ZAG mRNA (11.731±4.033 vs 13.201±3.433, P<0.05) and ZAG protein (5.540±0.573 vs 6.163±1.779, P<0.05). The level of serum uric acid was correlated positively with the expressions of ZAG ( r=0.176) , BMI ( r=0.161) , SBP ( r=0.144) , DBP ( r=0.250) , BUN ( r=0.461) , CREA ( r=0.649) , and TG ( r=0.212) , but negatively with HDL ( r=-0.333) , all with statistically significant differences ( P<0.05) . Conclusion The expressions of ZAG mRNA and protein can be used as a new target for prevention and treatment of HUA and its related metabolic diseases.

High levels of Zinc-α-2-Glycoprotein among Omani AIDS patients on combined antiretroviral therapy

<p><b>OBJECTIVE</b>To investigate the levels of zinc-α-2-glycoprotein (ZAG) among Omani AIDS patients receiving combined antiretroviral therapy (cART).</p><p><b>METHODS</b>A total of 80 Omani AIDS patients (45 males and 35 females), average age of 36 years, who were receiving cART at the Sultan Qaboos University Hospital (SQUH), Muscat, Oman, were tested for the levels of ZAG. In addition, 80 healthy blood donors (46 males and 34 females), average age of 26 years, attending the SQUH Blood Bank, were tested in parallel as a control group. Measurement of the ZAG levels was performed using a competitive enzyme-linked immunosorbent assay and in accordance with the manufacturer's instructions.</p><p><b>RESULTS</b>The ZAG levels were found to be significantly higher among AIDS patients compared to the healthy individuals (P=0.033). A total of 56 (70%) of the AIDS patients were found to have higher levels of ZAG and 16 (20%) AIDS patients were found to have high ZAG levels, which are significantly (P>0.031) associated with weight loss.</p><p><b>CONCLUSIONS</b>ZAG levels are high among Omani AIDS patients on cART and this necessitates the measurement of ZAG on routine basis, as it is associated with weight loss.</p>

High levels of Zinc-α-2-Glycoprotein among Omani AIDS patients on combined antiretroviral therapy

Objective: To investigate the levels of zinc-α-2-glycoprotein (ZAG) among Omani AIDS patients receiving combined antiretroviral therapy (cART). Methods: A total of 80 Omani AIDS patients (45 males and 35 females), average age of 36 years, who were receiving cART at the Sultan Qaboos University Hospital (SQUH), Muscat, Oman, were tested for the levels of ZAG. In addition, 80 healthy blood donors (46 males and 34 females), average age of 26 years, attending the SQUH Blood Bank, were tested in parallel as a control group. Measurement of the ZAG levels was performed using a competitive enzyme-linked immunosorbent assay and in accordance with the manufacturer's instructions. Results: The ZAG levels were found to be significantly higher among AIDS patients compared to the healthy individuals (P=0.033). A total of 56 (70%) of the AIDS patients were found to have higher levels of ZAG and 16 (20%) AIDS patients were found to have high ZAG levels, which are significantly (P > 0.031) associated with weight loss. Conclusions: ZAG levels are high among Omani AIDS patients on cART and this necessitates the measurement of ZAG on routine basis, as it is associated with weight loss.

High levels of Zinc-α-2-Glycoprotein among Omani AIDS patients on combined antiretroviral therapy

Objective:To investigate the levels of zinc-α-2-glycoprotein (ZAG) among Omani AIDS patients receiving combined antiretroviral therapy (cART). Methods:A total of 80 Omani AIDS patients (45 males and 35 females), average age of 36 years, who were receiving cART at the Sultan Qaboos University Hospital (SQUH), Muscat, Oman, were tested for the levels of ZAG. In addition, 80 healthy blood donors (46 males and 34 females), average age of 26 years, attending the SQUH Blood Bank, were tested in parallel as a control group. Measurement of the ZAG levels was performed using a competitive enzyme-linked immunosorbent assay and in accordance with the manufacturer’s instructions. Results:The ZAG levels were found to be significantly higher among AIDS patients compared to the healthy individuals (P=0.033). A total of 56 (70%) of the AIDS patients were found to have higher levels of ZAG and 16 (20%) AIDS patients were found to have high ZAG levels, which are significantly (P>0.031) associated with weight loss. Conclusions:ZAG levels are high among Omani AIDS patients on cART and this necessitates the measurement of ZAG on routine basis, as it is associated with weight loss.

The correlation between zinc-α2-glycoprotein and adiponectin in population with different glucose tolerance / 中华内分泌代谢杂志

Objective To investigate the relationship of circulating zinc-α2-glycoprotein (ZAG) as well as adiponectin with adiposity and insulin resistance in humans.Methods Serum ZAG and adiponectin levels were determined by ELISA in 285 subjects with normal glucose tolerance (NGT),impaired glucose tolerance (IGT),and newly diagnosed cases with type 2 diabetes mellitus(T2DM).The relationships between circulating ZAG and insulin resistance or metabolic parameters were also explored.Results Circulating ZAG and adiponectin levels were all lower in T2 DM and IGT subjects than those in control subjects [ZAG:(37.14 ± 13.25 and 48.84 ± 18.74 vs 59.36 ± 16.20) mg/L,P＜0.05 or P＜0.01 ; adiponectin:(27.79 ± 11.23 and 33.00 ± 9.42 vs 41.81 ± 13.68) μg/L,P＜0.01].Circulating ZAG was correlated positively with high density lipoprotein-cholesterol and adiponectin (all P＜0.01),and inversely with body mass index,waist-hip ratio,FAT％,diastolic blood pressure,triglyceride,fasting blood glucose,fasting insulin,HbA1C,and homeostasis model assessment for insulin resistance(HOMA-IR,P＜0.05 or P＜0.01).By multivariate analysis,ZAG levels were independently associated with body mass index,HOMA-IR,diastolic blood pressure,and adiponectin (P＜0.05 or P＜0.01).Conclusions ZAG levels,associated with fat,insulin sensitivity,and adiponectin expression,are likely to play an important role in insulin resistance and energy homeostasis in humans.

Role of zinc-α2-glycoprotein in lipid metabolism in cancer cachexia / 中华临床营养杂志

Zinc-α2-glycoprotein (ZAG), a new adipokine, plays an important role in the development of cancer cachexia by decreasing lipid content in body via promoting lipid mobilization and utilization. The lipolytic effect of ZAG is achieved by increasing the activity of hormone sensitive lipase, activating β3 adrenergic receptors,and up-regulating cyclic adenosine monophosphate. In addition, ZAG increases adiponectin expression and decreases leptin expression in adipocytes and adipose tissue. The ZAG expression is regulated by glucocorticoid, peroxisome proliferator-activated receptor gamma agonist rosiglitazone, tumor necrosis factor-α and many other factors.ZAG can potentially be applied as a tumor marker, and may become a new target in the treatment of cancer cachexia.