Objective To evaluate the effect of low-dose insulin [1 U/(kg·d)] in combination with selenium [180 g/(kg·d)] on general physiological parameters and glucose transporter (GLUT4) level in skeletal muscle of s...Objective To evaluate the effect of low-dose insulin [1 U/(kg·d)] in combination with selenium [180 g/(kg·d)] on general physiological parameters and glucose transporter (GLUT4) level in skeletal muscle of streptozotocin (STZ)-induced diabetic rats. Methods Diabetic rats were treated with insulin,selenium,and insulin and selenium in combination for four weeks. The level of blood glucose was determined using One Touch SureStep Blood Glucose meter and the level of GLUT4 in skeletal muscle was examined by immunoblotting and immunohistochemistry. Results Our data showed that insulin in combination with selenium could significantly lower blood glucose level and restore the disturbance in GLUT4 level in skeletal muscle. Treatment with insulin was only partially effective in restoring diabetic alterations. Conclusion It can be concluded that there is a synergistic action between insulin and selenium,and that treatment of diabetic rats with combined doses of insulin and selenium is effective in the normalization of blood glucose level and correction of altered GLUT4 distribution in skeletal muscle of diabetic rats.展开更多
Glucose is used aerobically and anaerobically to generate energy for cells.Glucose transporters(GLUTs)are transmembrane proteins that transport glucose across the cell membrane.Insulin promotes glucose utilization in ...Glucose is used aerobically and anaerobically to generate energy for cells.Glucose transporters(GLUTs)are transmembrane proteins that transport glucose across the cell membrane.Insulin promotes glucose utilization in part through promoting glucose entry into the skeletal and adipose tissues.This has been thought to be achieved through insulin-induced GLUT4 translocation from intracellular compartments to the cell membrane,which increases the overall rate of glucose flux into a cell.The insulin-induced GLUT4 translocation has been investigated extensively.Recently,significant progress has been made in our understanding of GLUT4 expression and translocation.Here,we summarized the methods and reagents used to determine the expression levels of Slc2a4 mRNA and GLUT4 protein,and GLUT4 translocation in the skeletal muscle,adipose tissues,heart and brain.Overall,a variety of methods such real-time polymerase chain reaction,immunohistochemistry,fluorescence microscopy,fusion proteins,stable cell line and transgenic animals have been used to answer particular questions related to GLUT4 system and insulin action.It seems that insulininduced GLUT4 translocation can be observed in the heart and brain in addition to the skeletal muscle and adipocytes.Hormones other than insulin can induce GLUT4 translocation.Clearly,more studies of GLUT4 are warranted in the future to advance of our understanding of glucose homeostasis.展开更多
Currently,glucose transporter 4(GLUT4)has been considered as the key player for the insulin-stimulated glucose transport in the muscle and adipose tissues.The development of recombinant DNA techniques allows the creat...Currently,glucose transporter 4(GLUT4)has been considered as the key player for the insulin-stimulated glucose transport in the muscle and adipose tissues.The development of recombinant DNA techniques allows the creations of genetically knockout,knockdown and transgenic animals and cells for the study of GLUT4’s physiological functions.Here,we have used key words to search the PubMed and summarized the methods used in Slc2a4 gene knockout,GLUT4 knockdown and overexpression in the whole body and tissue specific manner.The whole body GLUT4-null mice have growth retardation,but normal glucose tolerance and basal glucose turnover rates.Compared with whole body Slc2a4 knockout mice,adipose and muscle double knockout mice have impaired insulin tolerance and glucose intolerance.The results of GLUT4 knockdown in 3T3-L1 adipocytes have shown that its expression is needed for lipogenesis after,but not during,differentiation.Transgenic mice with the whole body GLUT4 overexpression have normal body weight and lowered blood glucose level.The adipose tissue specific overexpression of GLUT4 leads to increases in mouse body weight and adipose tissue weight.The insulin-stimulated GLUT4 translocation in the skeletal muscle contributes to the regulation of glucose homeostasis.Data from both transgenic overexpression and tissue specific Slc2a4 knockout indicate that GLUT4 probably plays a role in the glucose uptake in the fasting state.More studies are warranted to use advanced molecular biology tools to decipher the roles of GLUT4 in the control of glucose homeostasis.展开更多
Objective: The main goal of the present study was to investigate the effect of iron supplementation on glucose transporter 4 expressions in adipose tissue and skeletal muscle in female rats during pregnancy. Methods: ...Objective: The main goal of the present study was to investigate the effect of iron supplementation on glucose transporter 4 expressions in adipose tissue and skeletal muscle in female rats during pregnancy. Methods: Twenty-four pregnant Sprague-Dawley rats were randomly divided into 2 groups: a control group with a standard diet (containing iron 150 mg/kg) and an iron-supplementation group with a high-iron diet (containing iron 700 mg/kg) from day 0 to day 21 of pregnancy. Intraperitoneal glucose tolerance test was performed on gestational day 19. On gestational day 21, all of the pregnant rats from each group were sacrificed. The mean neonatal weights were measured and samples of maternal intraabdominal adipose tissue and skeletal muscle were taken to measure the expression of Glucose Transporter 4 (GLUT4) mRNA and protein. Results: Glucose tolerance decreased significantly in the iron supplementation group compared to the control group. The mean neonatal weights in the iron supplementation group were higher than that in the control group. Levels of GLUT4 mRNA in the adipose tissue were reduced by the administrations of high-iron diet. The skeletal muscle GLUT4 mRNA levels were not changed significantly by iron supplementation. Expression of GLUT4 protein both in the adipose tissue and skeletal muscle reduced significantly. Conclusion: These results suggest that iron supplementation during pregnancy would increase neonatal weights and could decrease maternal glucose tolerance by interfering GLUT4 expression in adipose tissue and skeletal muscle of rats.展开更多
Insulin resistance is a hallmark of the metabolic syndrome and type 2 diabetes.Dysfunction of PI-3K/Akt signaling was involved in insulin resistance.Glucose transporter 4(GLUT4)is a keyfactor for glucose uptake in mus...Insulin resistance is a hallmark of the metabolic syndrome and type 2 diabetes.Dysfunction of PI-3K/Akt signaling was involved in insulin resistance.Glucose transporter 4(GLUT4)is a keyfactor for glucose uptake in muscle and adipose tissues,which is closely regulated by Pi-3K/Aktsignaling in response to insulin treatment.Low-power laser irradiation(LPLI)has been shown toregulate various physiological processes and induce the synthesis or release of multiple moleculessuch as growth factors,which(especially red and near infrared light)is mainly through theactivation of mitochondrial respiratory chain and the initiation of intracellular signaling path-ways.Nevertheless,it is unclear whether LPLI could promote glucose uptake through activationof PI-3K/Akt/GLUT4 signaling in 3T3L-1 adipocytes.In this study,we investigated how LPLIpromoted glucose uptake through activation of PI-3K/Akt/GLUT4 signaling path way.Here,we showed that GLUT4 was localized to the Golgi apparatus and translocated from cytoplasm tocytomembrane upon LPLI treatment in 3T3L-1 adipocytes,which enhanced glucose uptake.Moreover,we found that glucose uptake was mediated by the PI3-K/Akt2 signaling,but notAkt1 upon LPLI treatment with Akt isoforms gene silence and PI3-K/Akt inhibitors.Collec-tively,our results indicate that PI3-K/Akt2/GLUT4 signaling act as the key regulators forimprovement of glucose uptake under LPLI treatment in 3T3L-i adipocytes.More importantly,our findings suggest that activation of PI3-K/Akt2/GLUT4 signaling by LPLI may provideguidance in practical applications for promotion of glucose uptake in insulin-resistant adiposetissue.展开更多
Objective:To investigate the protein and messenger RNA expression of glucose transporter 4 in endometrium of women with polycystic ovary syndrome(PCOS),and to evaluate its change after three months treatment of metfor...Objective:To investigate the protein and messenger RNA expression of glucose transporter 4 in endometrium of women with polycystic ovary syndrome(PCOS),and to evaluate its change after three months treatment of metformin.Methods:Twenty-two patients with polycystic ovary syndrome(group A)and six non-PCOS infertile women(group B)were recruited in our hospital.The consent form was obtained from each patient.Endometrium and blood samples were obtained during the proliferative phase of the menstrual cycle.Reverse transcriptase-polymerase chain reaction(RT-PCR)and immunohistochemical method were applied to detect the expression of glucose transporter 4(GLUT4)in endometrium.All PCOS patients received monotherapy of metformin after endometrium biopsy.Seven un-conceived patients(group A1)from group A who completed three months of metformin treatment were selected to perform the second time biopsy during proliferative phase.The expression of GLUT4 were remeasured as well.Results:There were no significant differences of the levels of E2,P and endometrium thickness on the biopsy day between group A and group B.But the basal levels of LH,T,LH/FSH ratio,and the ovarian volume were significantly higher in group A as compared with group B(P<0.001).The expression of GLUT4 in group A was significantly lower than that of group B(1.05±0.13 vs 1.50±0.21,P<0.001).In group A1,the expression of GLUT4 in endometrium were changed from 1.08±0.08 to 1.27±0.16 before and after treatment(P<0.05).The results of immunohistochemical staining of GLUT4 in endometrium were coincident with the results of RT-PCR.The fast insulin level and the insulin sensitivity index were also improved obviously after three months of metformin therapy(P<0.05).Conclusions:Insulin-resistance status was proved existing in endometrium of PCOS women;A significant improvement of GLUT4 expression was observed in endometrium after metformin treatment,supporting that metformin can relief insulin-resistant status of the endometrium in PCOS patients.展开更多
目的:观察磷酸西格列汀联合阿卡波糖对老年2型糖尿病患者血糖、血脂及葡萄糖转运蛋白4(GLUT4)的影响。方法:86例2型糖尿病老年患者随机分为对照组和观察组,每组43例。两组患者均给予饮食、运动、生活规律等方面的指导,并进行心理及用药...目的:观察磷酸西格列汀联合阿卡波糖对老年2型糖尿病患者血糖、血脂及葡萄糖转运蛋白4(GLUT4)的影响。方法:86例2型糖尿病老年患者随机分为对照组和观察组,每组43例。两组患者均给予饮食、运动、生活规律等方面的指导,并进行心理及用药方面的护理。在此基础上,对照组患者给予阿卡波糖片50 mg/次,每日3次,餐时咀嚼服用;观察组患者给予阿卡波糖片(用法用量同对照组)+磷酸西格列汀片100 mg/次,每日1次,口服。两组疗程均为3个月。比较两组患者治疗前后的空腹血糖(FBG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(Hb Alc)、体质量指数(BMI)、空腹胰岛素(FINs)、胰岛素抵抗指数(HOMA-IR)、胰岛B细胞功能指数(HOMA-B)、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)等指标,同时记录治疗期间不良反应发生情况。此外,选取43名健康志愿者作为健康对照组,分别比较两组患者治疗前后血清GLUT4水平与健康对照组之间的差别。结果:治疗后,两组患者BMI、FBG、2 h PG、HbA_lc、HOMA-IR、FINs、TC、TG、LDL-C水平显著低于同组治疗前,且观察组显著低于对照组;两组患者HOMA-B、HDL-C水平显著高于同组治疗前,且观察组显著高于对照组,差异均有统计学意义(P<0.05)。治疗前,两组患者血清GLUT4水平显著低于健康对照组,差异有统计学意义(P<0.05)。治疗后,对照组患者血清GLUT4水平与治疗前比较差异无统计学意义(P>0.05),观察组患者血清GLUT4水平显著高于同组治疗前,亦显著高于同期对照组,但仍低于健康对照组,差异均有统计学意义(P<0.05)。两组患者不良反应发生率比较差异无统计学意义(P>0.05)。结论:磷酸西格列汀联合阿卡波糖治疗老年2型糖尿病能有效控制患者的血糖和血脂水平、改善胰岛B细胞的功能、提高血清GLUT4水平,且不增加不良反应的发生,安全性较好。展开更多
基金supported by the National Basic Research Program of China (973Program) ( No.2007CB512005)the National Natural Science Foundation of China (No.30770785)+1 种基金the Cultivation Fund of the Key Scientific and Technological Innovation Pro-ject of the Ministry of Education of China (No.705045)the Specialized Research Fund for the Doctoral Program of Higher Education(No.20050698012)
文摘Objective To evaluate the effect of low-dose insulin [1 U/(kg·d)] in combination with selenium [180 g/(kg·d)] on general physiological parameters and glucose transporter (GLUT4) level in skeletal muscle of streptozotocin (STZ)-induced diabetic rats. Methods Diabetic rats were treated with insulin,selenium,and insulin and selenium in combination for four weeks. The level of blood glucose was determined using One Touch SureStep Blood Glucose meter and the level of GLUT4 in skeletal muscle was examined by immunoblotting and immunohistochemistry. Results Our data showed that insulin in combination with selenium could significantly lower blood glucose level and restore the disturbance in GLUT4 level in skeletal muscle. Treatment with insulin was only partially effective in restoring diabetic alterations. Conclusion It can be concluded that there is a synergistic action between insulin and selenium,and that treatment of diabetic rats with combined doses of insulin and selenium is effective in the normalization of blood glucose level and correction of altered GLUT4 distribution in skeletal muscle of diabetic rats.
基金We would like to thank the Department of Nutrition at the University of Tennessee at Knoxville for financial support to T.W.G.C.would like to thank Yantai Zestern Biotechnique Co.LTD for the research funding support.
文摘Glucose is used aerobically and anaerobically to generate energy for cells.Glucose transporters(GLUTs)are transmembrane proteins that transport glucose across the cell membrane.Insulin promotes glucose utilization in part through promoting glucose entry into the skeletal and adipose tissues.This has been thought to be achieved through insulin-induced GLUT4 translocation from intracellular compartments to the cell membrane,which increases the overall rate of glucose flux into a cell.The insulin-induced GLUT4 translocation has been investigated extensively.Recently,significant progress has been made in our understanding of GLUT4 expression and translocation.Here,we summarized the methods and reagents used to determine the expression levels of Slc2a4 mRNA and GLUT4 protein,and GLUT4 translocation in the skeletal muscle,adipose tissues,heart and brain.Overall,a variety of methods such real-time polymerase chain reaction,immunohistochemistry,fluorescence microscopy,fusion proteins,stable cell line and transgenic animals have been used to answer particular questions related to GLUT4 system and insulin action.It seems that insulininduced GLUT4 translocation can be observed in the heart and brain in addition to the skeletal muscle and adipocytes.Hormones other than insulin can induce GLUT4 translocation.Clearly,more studies of GLUT4 are warranted in the future to advance of our understanding of glucose homeostasis.
文摘Currently,glucose transporter 4(GLUT4)has been considered as the key player for the insulin-stimulated glucose transport in the muscle and adipose tissues.The development of recombinant DNA techniques allows the creations of genetically knockout,knockdown and transgenic animals and cells for the study of GLUT4’s physiological functions.Here,we have used key words to search the PubMed and summarized the methods used in Slc2a4 gene knockout,GLUT4 knockdown and overexpression in the whole body and tissue specific manner.The whole body GLUT4-null mice have growth retardation,but normal glucose tolerance and basal glucose turnover rates.Compared with whole body Slc2a4 knockout mice,adipose and muscle double knockout mice have impaired insulin tolerance and glucose intolerance.The results of GLUT4 knockdown in 3T3-L1 adipocytes have shown that its expression is needed for lipogenesis after,but not during,differentiation.Transgenic mice with the whole body GLUT4 overexpression have normal body weight and lowered blood glucose level.The adipose tissue specific overexpression of GLUT4 leads to increases in mouse body weight and adipose tissue weight.The insulin-stimulated GLUT4 translocation in the skeletal muscle contributes to the regulation of glucose homeostasis.Data from both transgenic overexpression and tissue specific Slc2a4 knockout indicate that GLUT4 probably plays a role in the glucose uptake in the fasting state.More studies are warranted to use advanced molecular biology tools to decipher the roles of GLUT4 in the control of glucose homeostasis.
文摘Objective: The main goal of the present study was to investigate the effect of iron supplementation on glucose transporter 4 expressions in adipose tissue and skeletal muscle in female rats during pregnancy. Methods: Twenty-four pregnant Sprague-Dawley rats were randomly divided into 2 groups: a control group with a standard diet (containing iron 150 mg/kg) and an iron-supplementation group with a high-iron diet (containing iron 700 mg/kg) from day 0 to day 21 of pregnancy. Intraperitoneal glucose tolerance test was performed on gestational day 19. On gestational day 21, all of the pregnant rats from each group were sacrificed. The mean neonatal weights were measured and samples of maternal intraabdominal adipose tissue and skeletal muscle were taken to measure the expression of Glucose Transporter 4 (GLUT4) mRNA and protein. Results: Glucose tolerance decreased significantly in the iron supplementation group compared to the control group. The mean neonatal weights in the iron supplementation group were higher than that in the control group. Levels of GLUT4 mRNA in the adipose tissue were reduced by the administrations of high-iron diet. The skeletal muscle GLUT4 mRNA levels were not changed significantly by iron supplementation. Expression of GLUT4 protein both in the adipose tissue and skeletal muscle reduced significantly. Conclusion: These results suggest that iron supplementation during pregnancy would increase neonatal weights and could decrease maternal glucose tolerance by interfering GLUT4 expression in adipose tissue and skeletal muscle of rats.
基金supported by the National Basic Research Program of China(2011CB910402,2010CB732602)the Program for Changjiang Scholars and Innovative Research Team in Uni-versity(IRT0829)the National Natural Science Foundation of China(81101741).
文摘Insulin resistance is a hallmark of the metabolic syndrome and type 2 diabetes.Dysfunction of PI-3K/Akt signaling was involved in insulin resistance.Glucose transporter 4(GLUT4)is a keyfactor for glucose uptake in muscle and adipose tissues,which is closely regulated by Pi-3K/Aktsignaling in response to insulin treatment.Low-power laser irradiation(LPLI)has been shown toregulate various physiological processes and induce the synthesis or release of multiple moleculessuch as growth factors,which(especially red and near infrared light)is mainly through theactivation of mitochondrial respiratory chain and the initiation of intracellular signaling path-ways.Nevertheless,it is unclear whether LPLI could promote glucose uptake through activationof PI-3K/Akt/GLUT4 signaling in 3T3L-1 adipocytes.In this study,we investigated how LPLIpromoted glucose uptake through activation of PI-3K/Akt/GLUT4 signaling path way.Here,we showed that GLUT4 was localized to the Golgi apparatus and translocated from cytoplasm tocytomembrane upon LPLI treatment in 3T3L-1 adipocytes,which enhanced glucose uptake.Moreover,we found that glucose uptake was mediated by the PI3-K/Akt2 signaling,but notAkt1 upon LPLI treatment with Akt isoforms gene silence and PI3-K/Akt inhibitors.Collec-tively,our results indicate that PI3-K/Akt2/GLUT4 signaling act as the key regulators forimprovement of glucose uptake under LPLI treatment in 3T3L-i adipocytes.More importantly,our findings suggest that activation of PI3-K/Akt2/GLUT4 signaling by LPLI may provideguidance in practical applications for promotion of glucose uptake in insulin-resistant adiposetissue.
文摘Objective:To investigate the protein and messenger RNA expression of glucose transporter 4 in endometrium of women with polycystic ovary syndrome(PCOS),and to evaluate its change after three months treatment of metformin.Methods:Twenty-two patients with polycystic ovary syndrome(group A)and six non-PCOS infertile women(group B)were recruited in our hospital.The consent form was obtained from each patient.Endometrium and blood samples were obtained during the proliferative phase of the menstrual cycle.Reverse transcriptase-polymerase chain reaction(RT-PCR)and immunohistochemical method were applied to detect the expression of glucose transporter 4(GLUT4)in endometrium.All PCOS patients received monotherapy of metformin after endometrium biopsy.Seven un-conceived patients(group A1)from group A who completed three months of metformin treatment were selected to perform the second time biopsy during proliferative phase.The expression of GLUT4 were remeasured as well.Results:There were no significant differences of the levels of E2,P and endometrium thickness on the biopsy day between group A and group B.But the basal levels of LH,T,LH/FSH ratio,and the ovarian volume were significantly higher in group A as compared with group B(P<0.001).The expression of GLUT4 in group A was significantly lower than that of group B(1.05±0.13 vs 1.50±0.21,P<0.001).In group A1,the expression of GLUT4 in endometrium were changed from 1.08±0.08 to 1.27±0.16 before and after treatment(P<0.05).The results of immunohistochemical staining of GLUT4 in endometrium were coincident with the results of RT-PCR.The fast insulin level and the insulin sensitivity index were also improved obviously after three months of metformin therapy(P<0.05).Conclusions:Insulin-resistance status was proved existing in endometrium of PCOS women;A significant improvement of GLUT4 expression was observed in endometrium after metformin treatment,supporting that metformin can relief insulin-resistant status of the endometrium in PCOS patients.
文摘目的:观察磷酸西格列汀联合阿卡波糖对老年2型糖尿病患者血糖、血脂及葡萄糖转运蛋白4(GLUT4)的影响。方法:86例2型糖尿病老年患者随机分为对照组和观察组,每组43例。两组患者均给予饮食、运动、生活规律等方面的指导,并进行心理及用药方面的护理。在此基础上,对照组患者给予阿卡波糖片50 mg/次,每日3次,餐时咀嚼服用;观察组患者给予阿卡波糖片(用法用量同对照组)+磷酸西格列汀片100 mg/次,每日1次,口服。两组疗程均为3个月。比较两组患者治疗前后的空腹血糖(FBG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(Hb Alc)、体质量指数(BMI)、空腹胰岛素(FINs)、胰岛素抵抗指数(HOMA-IR)、胰岛B细胞功能指数(HOMA-B)、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)等指标,同时记录治疗期间不良反应发生情况。此外,选取43名健康志愿者作为健康对照组,分别比较两组患者治疗前后血清GLUT4水平与健康对照组之间的差别。结果:治疗后,两组患者BMI、FBG、2 h PG、HbA_lc、HOMA-IR、FINs、TC、TG、LDL-C水平显著低于同组治疗前,且观察组显著低于对照组;两组患者HOMA-B、HDL-C水平显著高于同组治疗前,且观察组显著高于对照组,差异均有统计学意义(P<0.05)。治疗前,两组患者血清GLUT4水平显著低于健康对照组,差异有统计学意义(P<0.05)。治疗后,对照组患者血清GLUT4水平与治疗前比较差异无统计学意义(P>0.05),观察组患者血清GLUT4水平显著高于同组治疗前,亦显著高于同期对照组,但仍低于健康对照组,差异均有统计学意义(P<0.05)。两组患者不良反应发生率比较差异无统计学意义(P>0.05)。结论:磷酸西格列汀联合阿卡波糖治疗老年2型糖尿病能有效控制患者的血糖和血脂水平、改善胰岛B细胞的功能、提高血清GLUT4水平,且不增加不良反应的发生,安全性较好。
