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Insulin gene enhancer protein 1 mediates glycolysis and tumorigenesis of gastric cancer through regulating glucose transporter 4

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Cancer Communications 2021年第3期41卷 258-272页

作者： Ting Guo Yan-Hua Bai Xiao-Jing Cheng Hai-Bo Han Hong Du Ying Hu Shu-Qin Jia Xiao-Fang Xing Jia-Fu Ji Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Division of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital&InstituteBeijing 100142P.R.China Department of Pathology Peking University Cancer Hospital&InstituteBeijing 100142P.R.China The Tissue Bank Peking University Cancer Hospital&InstituteBeijing 100142P.R.China Department of Molecular Diagnosis Peking University Cancer Hospital&InstituteBeijing 100142P.R.China Department of Gastrointestinal Surgery Peking University Cancer Hospital&InstituteBeijing 100142P.R.China

Background:Insulin gene enhancer protein 1,(ISL1),a LIM-homeodomain transcription factor,is involved in multiple tumors and is associated with insulin secretion and metabolic ***,the role of ISL1 in stimulating glycolysis to promote tumorigenesis in gastric cancer(GC)is *** this study,we aimed to characterize the expression pattern of ISL1 in GC patients and explore its molecular biological mechanism in glycolysis and ***:We analyzed the expression and clinical significance of ISL1 in GC using immunohistochemistry and real-time polymerase chain reaction(PCR).Flow cytometry and IncuCyte assays were used to measure cell proliferation after ISL1 ***-sequencing was performed to identify differentially expressed genes,followed by Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis and Gene Set Enrichment Analysis(GSEA)to reveal key signaling pathways likely regulated by ISL1 in *** of the glycolytic ability of GC cells with ISL1 knockdown was validated by measuring the extracellular acidification rate(ECAR)and oxygen consumption rate(OCR)and by detecting glucose consumption and lactate *** expression of glucose transporter 4(GLUT4)and ISL1 was assessed by Western blotting,immunohistochemistry,and immunofluorescent *** luciferase reporter activity and chromatin immunoprecipitation assays were performed to determine the transcriptional regulation of ISL1 on ***:High levels of ISL1 and GLUT4 expression was associated with short survival of GC ***1 knockdown inhibited cell proliferation both in vitro and in *** analysis and GSEA for RNA-sequencing data indicated impairment of the glycolysis pathway in GC cells with ISL1 knockdown,which was validated by reduced glucose uptake and lactate production,decreased ECAR,and increased *** investigation indicated that ISL1 transcriptionally regulated GLUT4 through binding to its ***:ISL1 facilitates

关键词： gastric cancer glucose transporter 4 glycolysis insulin gene enhancer protein 1 tumorigenesis

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Uses of knockout,knockdown,and transgenic models in the studies of glucose transporter 4

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World Journal of Meta-Analysis 2022年第1期10卷 1-11页

作者： Tian-Nan Wang Xin-Ge Hu Guo-Xun Chen Department of Nutrition The University of TennesseeKnoxvilleTN 37996United States

Currently,glucose transporter 4(GLUT4)has been considered as the key player for the insulin-stimulated glucose transport in the muscle and adipose *** development of recombinant DNA techniques allows the creations of genetically knockout,knockdown and transgenic animals and cells for the study of GLUT4’s physiological ***,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 *** whole body GLUT4-null mice have growth retardation,but normal glucose tolerance and basal glucose turnover *** with whole body Slc2a4 knockout mice,adipose and muscle double knockout mice have impaired insulin tolerance and glucose *** results of GLUT4 knockdown in 3T3-L1 adipocytes have shown that its expression is needed for lipogenesis after,but not during,*** mice with the whole body GLUT4 overexpression have normal body weight and lowered blood glucose *** adipose tissue specific overexpression of GLUT4 leads to increases in mouse body weight and adipose tissue *** insulin-stimulated GLUT4 translocation in the skeletal muscle contributes to the regulation of glucose *** from both transgenic overexpression and tissue specific Slc2a4 knockout indicate that GLUT4 probably plays a role in the glucose uptake in the fasting *** studies are warranted to use advanced molecular biology tools to decipher the roles of GLUT4 in the control of glucose homeostasis.

关键词： glucose transporter 4 Knockout Knockdown Transgene Overexpression Insulin

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Effect of Huanglian Jiedu Decoction (黄连解毒汤) on glucose transporter 4 Expression in Adipose and Skeletal Muscle Tissues of Insulin Resistant Rats

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Chinese Journal of Integrative Medicine 2007年第1期13卷 41-45页

作者：陈广陆付耳金丹徐丽君王开富 Institute of Integrative Traditional Chinese and Western Medicine Tongji Hospital Tongji Medical College Huazhong University of Science and Technology

Objective： To investigate the effects of Huanglian Jiedu Decoction （黄连解毒汤, HLJDD） on glucose transporter 4 （GLUT4） protein expressions in insulin-resistant murine target tissues. Methods： The experimental male Wistar rats were established into insulin resistant models by injecting streptozotocin （STZ 30 mg/kg） via caudal vein and feeding them with high fat high caloric diet, and randomly divided into the model group, the aspirin group and the HLJDD group. Besides, a normal group was set up for control. Changes of body weight （BW）, levels of serum fasting blood glucose （FBG）, serum fasting insulin （FINS） and oral glucose tolerance test （OGTT） were routinely determined. The expression of GLUT4 protein in adipose and skeletal muscle tissues before and after insulin stimulation was determined with Western blot. Results： In the HLJDD group after treatment, BW and FBG got decreased, OGTT improved, and the expression and translocation of GLUT4 protein elevated obviously, either before or after insulin stimulation, as compared with those in the model group, showing significant differences respectively. Conclusion： The mechanism of improving insulin resistance by HLJDD is probably associated with its effect in elevating GLUT4 protein expression and translocation in adipose and skeletal muscle tissues of insulin resistant rats.

关键词： Huanglian Jiedu Decoction glucose transporter 4 insulin resistance target tissue

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Current understanding of glucose transporter 4 expression and functional mechanisms

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World Journal of Biological Chemistry 2020年第3期11卷 76-98页

作者： Tiannan Wang Jing Wang Xinge Hu Xian-Ju Huang Guo-Xun Chen Department of Nutrition The University of TennesseeKnoxvilleTN 37996United States College of Pharmacy South-Central University for NationalitiesWuhan 430074Hubei ProvinceChina

glucose is used aerobically and anaerobically to generate energy for *** transporters(GLUTs)are transmembrane proteins that transport glucose across the cell *** promotes glucose utilization in part through promoting glucose entry into the skeletal and adipose *** 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 *** insulin-induced GLUT4 translocation has been investigated ***,significant progress has been made in our understanding of GLUT4 expression and ***,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 ***,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 *** seems that insulininduced GLUT4 translocation can be observed in the heart and brain in addition to the skeletal muscle and *** other than insulin can induce GLUT4 ***,more studies of GLUT4 are warranted in the future to advance of our understanding of glucose homeostasis.

关键词： glucose transporter 4 Insulin Skeletal muscle Adipocytes Brain Heart Antibodies

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Anti-diabetic effects of cinnamaldehyde and berberine and their impacts on retinol-binding protein 4 expression in rats with type 2 diabetes mellitus

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Chinese Medical Journal 2008年第21期121卷 2124-2128页

作者： ZHANG Wei XU Yan-cheng GUO Fang-jian MENG Ye LI Ming-li Department of Endocrinology Zhongnan Hospital ot Wunan University Wuhan Hubei 430071 China

Background Retinol binding protein 4 （RBP4）, as an adipocyte secreted cytokine, was recently found to be inversely correlated with expression of glucose transporter 4 （GLUT4） in insulin resistance （IR） state and to have an intimate relationship with IR and type 2 diabetes mellitus （T2DM）. The present study aimed to evaluate the anti-diabetic efficacy of cinnamaldehyde （Cin）, berberine （Ber）, and metformin （Met） as well as their impacts on the RBP4-GLUT4 system. Methods Rat models of T2DM were established by combination of intraperitoneal injection of low-dose streptozotocin and high fat diet induction. Rats were divided into five groups： the control group, the diabetes group, the diabetes＋Ber group, the diabetes＋Cin group, and the diabetes＋Met group. Western blotting was used to detect the serum or tissue RBP4 and GLUT4 protein levels. Results After treatment for four weeks, both Cin and Ber displayed significant hypolipidemic, hypoglycemic, and insulin sensitizing functions （P 〈0.01） compared with the control group. Their effects on lowering fasting plasma glucose （FPG）, low density lipoprotein-cholesterol （LDL-C） and homeostasis model assessment of insulin resistance （HOMA-IR） seem even better than that of Met. Cin and Ber markedly lowered serum RBP4 levels and up-regulated the expression of tissue GLUT4 protein, and Cin seemed more notable in affecting these two proteins. Conclusions Both Cin and Ber display an exciting anti-diabetic efficacy in this study and may be of great value for the treatment of type 2 diabetes. Their mechanisms involve the RBP4-GLUT4 system, during which the serum RBP4 levels are lowered and the expression of tissue GLUT4 protein is up-regulated.

关键词： cinnamaldehyde berberine type 2 diabetes meUitus insulin resistance retinol binding protein 4 glucose transporter 4

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