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
BACKGROUND Sodium-dependent glucose transporter 2 inhibitors(SGLT2i)have shown efficacy in reducing heart failure(HF)burden in a very heterogeneous groups of patients,raising doubts about some contemporary assumptions...BACKGROUND Sodium-dependent glucose transporter 2 inhibitors(SGLT2i)have shown efficacy in reducing heart failure(HF)burden in a very heterogeneous groups of patients,raising doubts about some contemporary assumptions of their mechanism of action.We previously published a prospective observational study that evaluated mechanisms of action of SGLT2i in patients with type 2 diabetes who were in HF stages A and B on dual hypoglycemic therapy.Two groups of patients were included in the study:the ones receiving SGLT2i as an add-on agent to metformin and the others on dipeptidyl peptidase-4 inhibitors as an add-on to metformin due to suboptimal glycemic control.AIM To evaluate the outcomes regarding natriuretic peptide,oxidative stress,inflammation,blood pressure,heart rate,cardiac function,and body weight.METHODS The study outcomes were examined by dividing each treatment arm into two subgroups according to baseline parameters of global longitudinal strain(GLS),N-terminal pro-brain natriuretic peptide,myeloperoxidase(MPO),high-sensitivity C-reactive protein(hsCRP),and systolic and diastolic blood pressure.To evaluate the possible predictors of observed changes in the SGLT2i arm during follow-up,a rise in stroke volume index,body mass index(BMI)decrease,and lack of heart rate increase,linear regression analysis was performed.RESULTS There was a greater reduction of MPO,hsCRP,GLS,and blood pressure in the groups with higher baseline values of mentioned parameters irrespective of the therapeutic arm after 6 months of follow-up.Significant independent predictors of heart rate decrease were a reduction in early mitral inflow velocity to early diastolic mitral annular velocity at the interventricular septal annulus ratio and BMI,while the predictor of stroke volume index increase was SGLT2i therapy itself.CONCLUSION SGLT2i affect body composition,reduce cardiac load,improve diastolic/systolic function,and attenuate the sympathetic response.Glycemic control contributes to the improvement of heart function,blood pressure control,oxidative stress,and reduction in inflammation.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
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
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
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
Background: This study investigated serum Glucose transporter (GLUT) 4 levels and examined the relationship between serum GLUT4 levels and sepsis in critically ill children. Methods: This was a retrospective study of ...Background: This study investigated serum Glucose transporter (GLUT) 4 levels and examined the relationship between serum GLUT4 levels and sepsis in critically ill children. Methods: This was a retrospective study of 77 critically ill children and 33 non-diabetic healthy children (controls) who were admitted between 07/2015 and 05/2016. Patient data, clinical information, and blood samples were collected on admission, alongside a large number of laboratory parameters that were routinely assessed. Critically ill patients were divided into sepsis and non-sepsis/systemic inflammatory response syndrome (SIRS). Serum GLUT4 was measured using western blotting and enzyme-linked immunosorbent assays. Insulin resistance indexes, clinical data, laboratory parameters, and inflammatory cytokines were assessed. Results: GLUT4 serum levels were higher in critically ill children than in healthy children (90.5 vs. 30.3 μg/L, P 0.05). Compared to healthy children, hyperglycemic patients (n = 48) had elevated GLUT4 serum levels (30.3 vs. 103.7 g/L, P Conclusions: GLUT4 serum levels might be significantly increased in critically ill children compared with healthy children, particularly those in septic shock. Serum GLUT4 could predict disease severity.展开更多
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BACKGROUND Sodium-dependent glucose transporter 2 inhibitors(SGLT2i)have shown efficacy in reducing heart failure(HF)burden in a very heterogeneous groups of patients,raising doubts about some contemporary assumptions of their mechanism of action.We previously published a prospective observational study that evaluated mechanisms of action of SGLT2i in patients with type 2 diabetes who were in HF stages A and B on dual hypoglycemic therapy.Two groups of patients were included in the study:the ones receiving SGLT2i as an add-on agent to metformin and the others on dipeptidyl peptidase-4 inhibitors as an add-on to metformin due to suboptimal glycemic control.AIM To evaluate the outcomes regarding natriuretic peptide,oxidative stress,inflammation,blood pressure,heart rate,cardiac function,and body weight.METHODS The study outcomes were examined by dividing each treatment arm into two subgroups according to baseline parameters of global longitudinal strain(GLS),N-terminal pro-brain natriuretic peptide,myeloperoxidase(MPO),high-sensitivity C-reactive protein(hsCRP),and systolic and diastolic blood pressure.To evaluate the possible predictors of observed changes in the SGLT2i arm during follow-up,a rise in stroke volume index,body mass index(BMI)decrease,and lack of heart rate increase,linear regression analysis was performed.RESULTS There was a greater reduction of MPO,hsCRP,GLS,and blood pressure in the groups with higher baseline values of mentioned parameters irrespective of the therapeutic arm after 6 months of follow-up.Significant independent predictors of heart rate decrease were a reduction in early mitral inflow velocity to early diastolic mitral annular velocity at the interventricular septal annulus ratio and BMI,while the predictor of stroke volume index increase was SGLT2i therapy itself.CONCLUSION SGLT2i affect body composition,reduce cardiac load,improve diastolic/systolic function,and attenuate the sympathetic response.Glycemic control contributes to the improvement of heart function,blood pressure control,oxidative stress,and reduction in inflammation.
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.
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.
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Background: This study investigated serum Glucose transporter (GLUT) 4 levels and examined the relationship between serum GLUT4 levels and sepsis in critically ill children. Methods: This was a retrospective study of 77 critically ill children and 33 non-diabetic healthy children (controls) who were admitted between 07/2015 and 05/2016. Patient data, clinical information, and blood samples were collected on admission, alongside a large number of laboratory parameters that were routinely assessed. Critically ill patients were divided into sepsis and non-sepsis/systemic inflammatory response syndrome (SIRS). Serum GLUT4 was measured using western blotting and enzyme-linked immunosorbent assays. Insulin resistance indexes, clinical data, laboratory parameters, and inflammatory cytokines were assessed. Results: GLUT4 serum levels were higher in critically ill children than in healthy children (90.5 vs. 30.3 μg/L, P 0.05). Compared to healthy children, hyperglycemic patients (n = 48) had elevated GLUT4 serum levels (30.3 vs. 103.7 g/L, P Conclusions: GLUT4 serum levels might be significantly increased in critically ill children compared with healthy children, particularly those in septic shock. Serum GLUT4 could predict disease severity.
