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ABSTRACT The prevalence of nephrolithiasis is increasing worldwide. Despite advances in understanding the pathogenesis of lithiasis, few studies have demonstrated that specific clinical interventions reduce the recurrence of nephrolithiasis. The aim of this review is to analyze the current data and potential effects of iSGLT2 in lithogenesis and try to answer the question: Should we also "gliflozin" our patients with kidney stone disease?
RESUMO A prevalência da nefrolitíase está aumentando em todo o mundo. Apesar dos avanços na compreensão da patogênese da doença litiásica, poucos estudos demonstraram que intervenções clínicas específicas diminuem a recorrência da nefrolitíase. O objetivo desta revisão é analisar os dados atuais e efeitos potenciais dos iSGLT2 na doença litiásica e tentar responder à pergunta: devemos também "gliflozinar" os litiásicos?
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SUMMARY: Glucose has an essential role in the proliferation and survival of testicular tissue. Glucose transporters (GLUTs) are responsible for glucose uptake across cell membranes. In the present work, two main isoforms GLUT1 and GLUT3 were investigated in the testes of Laboratory mouse (BALB/c), Lesser Egyptian jerboa (Jaculus jaculus), Golden hamster (Mesocricetus auratus), and Desert Hedgehog (Paraechinus aethiopicus). Immunofluorescent localization of GLUT1 and GLUT3 showed considerable species differences. The lowest expression of GLUT1 and GLUT3 was localized in the testis of Laboratory mouse (BALB/c), the highest GLUT1 localization was detected in the testis of Lesser Egyptian jerboa (Jaculus jaculus), and the highest GLUT3 immunofluorescent localization was observed in the testis of Hedgehog (Paraechinus aethiopicus). The results imply that GLUT3 is the principal glucose transporter in the studied testes, which is related to species differences. The different immunolocalization of GLUT in examined testes suggests using various transport systems for energy gain in different species.
La glucosa tiene un papel esencial en la proliferación y supervivencia del tejido testicular. Los transportadores de glucosa (GLUT) son responsables de la absorción de glucosa a través de las membranas celulares. En el presente trabajo, se investigaron dos isoformas principales GLUT1 y GLUT3 en los testículos de un ratón de laboratorio (BALB/c), un jerbo egipcio menor (Jaculus jaculus), un hámster dorado (Mesocricetus auratus) y un erizo del desierto (Paraechinus aethiopicus). La localización inmunofluorescente de GLUT1 y GLUT3 mostró diferencias considerables entre especies. La expresión más baja de GLUT1 y GLUT3 se localizó en el testículo del ratón de laboratorio (BALB/c), la localización más alta de GLUT1 se detectó en el testículo del jerbo egipcio menor (Jaculus jaculus) y la localización inmunofluorescente de GLUT3 más alta se observó en el testículo de Erizo (Paraechinus aethiopicus). Los resultados implican que GLUT3 es el principal transportador de glucosa en los testículos estudiados, lo que está relacionado con diferencias entre especies. La diferente inmunolocalización de GLUT en los testículos examinados sugiere el uso de varios sistemas de transporte para ganar energía en diferentes especies.
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Animales , Testículo/metabolismo , Transportador de Glucosa de Tipo 1/metabolismo , Transportador de Glucosa de Tipo 3/metabolismo , Mamíferos , Ratones Endogámicos BALB CRESUMEN
Introducción La diabetes mellitus tipo 2 es una enfermedad de alta prevalencia y está asociada a mayor morbimortalidad. Debido al bajo porcentaje de compensación, se han buscado nuevas estrategias de tratamiento farmacológico, como los inhibidores del cotransportador sodio-glucosa tipo 2. Objetivo Describir la evolución de pacientes diabéticos tipo 2 insulino-requirentes tratados con empagliflozina en el Hospital Peñaflor, ubicado en el sector poniente de la Región Metropolitana, Chile. El objetivo primario fue evaluar la eficacia del medicamento respecto a hemoglobina glicosilada A1c. Los objetivos secundarios fueron registrar el logro de hemoglobina glicosilada A1c igual o menor a 7,5% según análisis de supervivencia. Luego, consignar el cambio en la velocidad de filtración glomerular y en la excreción urinaria de albúmina post tratamiento. Métodos Revisión de ficha clínica de todos los pacientes tratados con empagliflozina desde noviembre de 2019 a junio de 2023. Media de seguimiento de 19 (de 16,3 a 40) meses. Para comparación entre valores de hemoglobina glicosilada A1c según rangos de seguimiento, se utilizó prueba T de Student de términos pareados o prueba de Wilcoxon. Resultados Se estudió a 58 pacientes, 15 hombres y 43 mujeres (74,1%). Edad 58,5 ± 9,2 años, rango de 35 a 75 años. Hemoglobina glicosilada A1c basal de 10,3 ± 1,6% y 8,98% ± 2,2 en un rango de seguimiento de 18 a 24 meses post tratamiento, resultando en un descenso de 1,27% (p = 0,002; intervalo de confianza 95%: 0,5 a 2,03). El efecto adverso más frecuente fue infección del tracto urinario. Conclusiones Los pacientes diabéticos tipo 2 insulino-requirentes tratados con empagliflozina en el Hospital Peñaflor lograron un mejor control glicémico con pocos efectos adversos.
Background Type 2 diabetes mellitus is a highly prevalent disease and is associated with increased morbidity and mortality. Due to the low percentage of adequate glycemic control, new strategies for the treatment of type 2 diabetes mellitus have been sought, including sodium-glucose cotransporter type 2 inhibitorss. Objective To describe the evolution of patients with type 2 diabetes mellitus with insulin requirements treated with empagliflozin at the Peñaflor Hospital. The primary objective was to evaluate the efficacy of the medication regarding glycosylated hemoglobin A1c (HbA1c). The secondary objectives were: 1) achievement of HbA1c equal to or less than 7.5% according to survival analysis. 2) Change in glomerular filtration rate and urinary albumin excretion post treatment. Methods Review of clinical records of all patients treated with empagliflozin from November 2019 to June 2023. Average follow-up of 19 (16.3 to 40) months. To compare HbA1c values according to follow-up ranges, the paired T test or Wilcoxon test was used. Results We included 58 patients, 15 men and 43 women (74.1%), with an average age of 58.5 ± 9.2 years, ranging from 35 to 75 years. Baseline HbA1c of 10.3 ± 1.6% and 8.98% ± 2.2 in a follow-up of 18 to 24 months post-treatment, resulted in a decrease of 1.27% (p = 0.002; confidence interval 95%: 0.5 to 2.03). The most common adverse effect was urinary tract infection. Conclusions Patients with type 2 diabetes mellitus with insulin requirements treated with empagliflozin at the Peñaflor Hospital achieved better glycemic control with few adverse effects.
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Tumor cells use glycolysis to provide material and energy under hypoxic conditions to meet the energy requirements for rapid growth and proliferation， namely the Warburg effect. Even under aerobic conditions， tumor cells mainly rely on glycolysis to provide energy. Therefore， glucose transporter protein 1（GLUT1）， which is involved in the process of glucose metabolism， plays an important role in tumorigenesis， development and drug resistance， and is considered to be one of the important targets in the treatment of malignant tumors. In recent years， research on tumor glucose metabolism has gradually become a hot spot. It has been shown that various factors are involved in the regulation of tumor energy metabolism， among which the role of GLUT1 is the most critical. In this paper， the authors reviewed the latest research progress of GLUT1-targeted traditional Chinese medicine（TCM） active ingredient nano-delivery system in tumor therapy， aiming to reveal the feasibility and effectiveness of this system in the delivery of chemotherapeutic drugs. The GLUT1-targeted TCM active ingredient nano-delivery system can overcome the bottleneck of the traditional targeting strategy as well as the high-permeability long retention（EPR） effect. In summary， the authors believe that the GLUT1-targeted TCM active ingredient nano-delivery system provides a new strategy for targeted treatment of tumors and has a broad application prospect in tumor prevention and treatment.
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Objective To investigate the effects of probiotics combined with dietary intervention on pe-ripheral blood glucose and lipid metabolism indicators,placental tissue insulin signaling pathway proteins ex-pression and pregnant outcome in the patients with gestational diabetes mellitus(GDM).Methods A total of 83 patients with GDM in this hospital from December 2021 to December 2022 were selected as the study sub-jects and divided into the probiotics group(probiotics combined with diet intervention,43 cases)and control group(simple diet intervention,40 cases)by the random number table method.The levels of peripheral blood glucose,lipid and insulin resistance related indicators before the intervention and in 8 weeks after the interven-tion were compared between the two groups.The histological changes of placenta were observed by HE stai-ning.The pathological indicators were compared between the two groups.The expression levels of insulin re-ceptor substrate-1(IRS-1),glucose transporter 4(GLUT4)and synaptosome-associated protein of 23 kDa(SNAP23)in placental tissue were detected by immunohistochemistry.The pregnant adverse outcomes were compared between the two groups,and the clinical efficacy of probiotics was evaluated.Results Compared with the control group,the levels of fasting blood glucose(FBG),fasting insulin(FINS),serum triglyceride(TG)and low density lipoprotein cholesterol(LDL-C)in 8 weeks after intervention in the probiotics group were significantly decreased(P＜0.05),and the level of serum high density lipoprotein cholesterol(HDL-C)was significantly increased(P＜0.05).There were no significant differences in the incidence rates of poor villi maturation,thickening of dry villi arterioles and capillary filling in villi interstitial between the two groups(P＞0.05).Compared with the control group,the expression levels of IRS-1,GLUT4 and SNAP23 in placen-tal tissue of the probiotics group were significantly increased(P＜0.05).The incidence rates of neonatal hy-poglycemia and neonatal hyperbilirubinemia in the probiotics group were significantly lower than those in the control group(P＜0.05).Conclusion Compared with simple dietary intervention,probiotics combined with dietary intervention has more advantages in improving glucose and lipid metabolism of GDM patients,moreo-ver reduces the adverse events occurrence in newborns.
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Objective To explore the changes in the expression of glucose transporters 1/4(GLUT1/4)and Sirtuins in the retina of rats with diabetes.Methods Twenty 8-week-old healthy male Sprague-Dawley rats were randomly divid-ed into normal control and diabetic groups.Rats in the diabetic group received a disposable intraperitoneal injection of 60 mg·kg-1 streptozotocin to induce the diabetes model,while rats in the normal control group were injected with an equiva-lent amount of solvent.Body weight and blood glucose were measured at 2-week intervals.At 12 weeks after modeling,color Doppler ultrasound was applied to detect blood flow parameters in the central retinal artery(CRA)of rats;after an-esthetizing rats with sodium pentobarbital,eyeballs were harvested,and the pathological changes of rat retinal tissue were observed by hematoxylin & eosin(HE)staining.The expression of messenger ribonucleic acid(mRNA)for GLUT 1/4 and Sirtuins in the retina of rats were detected by immunohistochemical staining,Western blot and quantitative of reverse tran-scription polymerase chain reaction(qRT-PCR),respectively.Results At 12 weeks after modeling,compared with the normal control group,peak systolic velocity and end diastolic velocity were significantly lower in CRA of rats in the diabetic group(both P＜0.001);there were no significant differences in resistance index and pulsatility index(both P＞0.05).The HE staining results at 12 weeks after modeling showed that rats in the normal control group had clear structure in each layer of retinal tissues,closely and regularly arranged cells,and no obvious pathological changes;rats in the diabetic group showed decreased retinal thickness,blurred boundary of each layer,disordered structure and reduced cell number.Immu-nohistochemical staining at 12 weeks after modeling showed that GLUT 1 was mainly located in the retinal pigment epithelial layer of rats,and GLUT 4 was located in the ganglion cell layer,inner plexiform layer and photoreceptor layer.Western blot results showed that the relative expression of GLUT1 and GLUT 4 protein in the diabetic group were lower than that in the normal control group(both P＜0.05),and the relative expression of SIRT1-SIRT7 protein in the retina of rats in the di-abetic group were lower than those of the normal control group(all P＜0.05).qRT-PCR showed a decreased relative ex-pression of SIRT1-SIRT7 mRNA in the retina of rats in the diabetic group compared with that of the normal control group(allP＜0.01).Conclusion Diabetes can cause altered expression of GLUT1/4 and Sirtuins in the retinal tissue of rats,and GLUT1/4 and Sirtuins may be involved in the occurrence and development of diabetic retinopathy.
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Objective To investigate the effect of Cyclocarya paliurus(Batal.)lljinskaja polysaccharides on insulin resistance in type 2 diabetic rats by regulating glucose transporter 4(GLUT4)translocation in islet and liver.Methods High-fat diet combined with low-dose streptozotocin(35 mg·kg-1)to induce type 2 diabetes model,all the rats were randomly divided into model control group,Cyclocarya paliurus polysaccharides groups(5,10 g·kg-1)and metformin group(0.25 g·kg-1),and treated for eight weeks(n=9 in each group).Fasting glucose and lipid were determined.Histopathology of rat islet and liver were observed by hematoxylin and eosin staining.Protein expressions of phosphorylated phosphoinositide-3-kinase(p-PI3K),phosphorylated serine-threonine kinase 1(p-Akt1),and GLUT4 in islet were measured by immunohistochemistry staining.GLUT4 translocation in the islet and liver was detected by immunofluorescence.Results Compared with the model control group,the Cyclocarya paliurus polysaccharides group and metformin group had declined fasting glucose levels and increased high-density lipoprotein(P＜0.05).The structure of the islets and liver was relatively complete.The content of p-PI3K,p-Akt1 and GLUT4 in the islet increased(P＜0.05).GLUT4 translocation in the liver and islet enhanced(P＜0.05).Conclusions Cyclocarya paliurus polysaccharides alleviate glucose and lipid metabolism disorders.The mechanism may lay in it activating protein expressions of p-PI3K,p-Akt1,and GLUT4 in islet cells.GLUT4 translocation to the islet and liver cell membrane are increased to regulate peripheral islet resistance.
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Objective To strengthen nursing awareness and attention,and improve the quality of medication and nursing care,Meta-analysis was used to evaluate the occurrence of sodium-glucose transporter 2 inhibitor related ketoacidosis.Methods Relevant randomized controlled trials were searched in 6 databases,such as CNKI,PubMed,Embase,and the Clinical trial platform,and the literature was screened based on inclusion and exclusion criteria.The search time was from the establishment of databases to January 2023.Revman 5.4.1 was used for quality evaluation and Meta-analysis.Results 24 randomized controlled trials were included.The Meta-analysis results showed that sodium-glucose transporter 2 inhibitors increased the incidence of ketoacidosis(RR=2.52,95％CI[1.82,3.49],P＜0.001).Subgroup analysis showed that the sodium-glucose transporter 2 inhibitors increased the incidence of ketoacidosis in patients with type 2 diabetes(RR=2.42,95％CI[1.70,3.43],P＜0.001),cardiovascular disease(RR=2.32,95％CI[1.59,3.39],P＜0.001),and chronic kidney disease(RR=2.82,95％CI[1.73,4.58],P＜0.001).Cargliflozin(RR=3.21,95％CI[1.43,7.18],P=0.005),Daggliflozin(RR=2.73,95％CI[1.51,4.93],P＜0.001),and Sogliflozin(RR=1.92,95％CI[1.06,3.50],P=0.030)increased the incidence of ketoacidosis,while Engliflozin(RR=1.80,95％CI[0.79,4.11],P=0.160)did not have a significant effect.When the eGFR of patients≤60(mUmin/1.73m2)(RR=2.74,95％CI[1.63,4.60],P＜0.001),the duration of medication≤ 12 month(RR=3.31,95％CI[1.79,6.12],P＜0.001),or the duration of medication＞12 month(RR=2.19,95％CI[1.23,3.91],P=0.008),the sodium-glucose transporter 2 inhibitors increased the occurrence of ketoacidosis.Conclusion For patients receiving sodium-glucose transporter 2 inhibitors treatment regardless of whether they are complicated with diabetes,especially those with heart and kidney diseases,in the early and middle stages of medication,with eGFR ≤60 ml/(min·1.73m2),and those with other susceptibility factors,we should strengthen the observation of patients'medication,optimize medication care,and early identify and intervene in the occurrence of ketoacidosis.
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Background Arsenic exposure is a common and important environmental and occupational hazardous factor in China, and arsenic-induced insulin resistance (IR) has attracted widespread attention as a negative health outcome to the population. Objective To explore part of the mechanism of hepatic IR induced by arsenic exposure based on the peroxisome proliferators-activated receptors γ (PPARγ)/ glucose transporter 4 (GLUT4) pathway, and to investigate potential effects of Ginkgo biloba extract (GBE) on hepatic IR induced by arsenic exposure and associated mechanism of action. Methods The target of drug action was predicted by network pharmacology and verified by in vivo and in vitro experiments. In vivo experiments: 48 SPF C57BL/6J male mice were divided into 4 groups, including control group, 50 mg·L−1 NaAsO2 model group (NaAsO2), 50 mg·L−1 NaAsO2+10 mg·kg−1 GBE intervene group (NaAsO2+GBE), and 10 mg·kg−1 GBE group (GBE), 12 mice in each group. The animals were given free access to purified water containing 50 mg·L−1 NaAsO2, or given intraperitoneal injection of normal saline containing 10 mg·kg−1 GBE once per week. After 6 months of exposure, blood glucose detection, intraperitoneal glucose tolerance test (IPGTT), and insulin tolerance test (ITT) were performed. Serum and liver tissues were collected after the mice were neutralized, liver histopathological sections were obtained, serum insulin levels, liver tissue glycogen content, glucose content were detected by enzyme linked immunosorbent assay (ELISA), and the expression of PPARγ and GLUT4 proteins was detected by Western blot (WB). In vitro experiments: HepG2 cells were divided into 4 groups, including control group, 8 μmol·L−1 NaAsO2 group (NaAsO2), 8 μmol·L−1 NaAsO2 + 200 mg·L−1 GBE intervene group (NaAsO2+GBE), and 200 mg·L−1 GBE group (GBE). The levels of glycogen and glucose were detected by ELISA, and the expression of PPARγ and GLUT4 proteins was detected by WB. Results A strong binding effect between GBE and PPARγ was revealed by network pharmacology. In in vivo experiments, the NaAsO2 group exhibited an elevated blood glucose compared to the control group, and the NaAsO2+GBE group showed a decreased blood glucose compared to the NaAsO2 group (P<0.01). The histopathological sections indicated severe liver structural damage in the arsenic exposure groups (NaAsO2 group and NaAsO2+GBE group), with varying staining intensity, partial liver cell necrosis, and diffuse red blood cell appearance. Both results of in vitro and in vivo experiments showed a decrease in glycogen synthesis and glucose uptake in the NaAsO2 groups compared to the control groups, which was alleviated in the NaAsO2+GBE group (P<0.01). The results of WB revealed inhibited PPARγ expression and reduced GLUT4 levels on the cell membrane, and all these changes were alleviated in the NaAsO2+GBE group (P<0.01). Conclusion This study findings suggest that GBE antagonizes arsenic exposure-induced hepatic IR by regulating the PPARγ/GLUT4 pathway, indicating that GBE has a protective effect on arsenic exposure-induced hepatic IR, and PPARγ may be a potential therapeutic target for arsenic exposure-induced hepatic IR.
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Resumen La insuficiencia cardiaca aguda es una emergencia que aumenta la mortalidad cardiovascular debido a los síntomas y signos de congestión e hipoperfusión vascular. El manejo actual con diuréticos, inotrópicos y vasopresores mejora el estado clínico; sin embargo, la morbimortalidad asociada a esta patología sigue siendo altamente significativa. Por otra parte, los inhibidores del cotransportador sodio-glucosa tipo 2 (iSGLT2) han demostrado una reducción en la hospitalización y mortalidad cardiovascular en los pacientes con insuficiencia cardiaca crónica. Por ende, el objetivo de este artículo es analizar los efectos clínicos de este grupo farmacológico en la insuficiencia cardiaca aguda, con base en investigaciones científicas. Los hallazgos de estas investigaciones demostraron un beneficio clínico de los iSGLT2 sobre esta patología, con base a parámetros como mortalidad, hospitalización, eventos clínicos, función renal, efecto diurético y concentraciones del biomarcador NT-proBnp, los cuales se detallarán en el presente artículo. Por consiguiente, se concluyó que estos fármacos son seguros sobre la evolución clínica de la insuficiencia cardiaca aguda.
Abstract Acute heart failure is an emergency that increases cardiovascular mortality due to symptoms and signs of vascular congestion and hypoperfusion. Current management with diuretics, inotropes, and vasopressors improves the clinical status; However, the morbidity and mortality associated with this pathology remains highly significant. On the other hand, sodium-glucose cotransporter 2 (SGLT2i) inhibitors have shown a reduction in hospitalization and cardiovascular mortality in patients with chronic heart failure. Therefore, the objective of this article is to analyze the clinical effects of this pharmacological group in acute heart failure, based on scientific research. The findings of these investigations demonstrated a clinical benefit of SGLT2i on this pathology, based on parameters such as mortality, hospitalization, clinical events, renal function, diuretic effect and concentrations of the NTproBnp biomarker, which will be detailed in this article. Therefore, it was concluded that these drugs are safe on the clinical course of acute heart failure.
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Humanos , Masculino , Femenino , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológicoRESUMEN
ABSTRACT Background: Critical illness is a major ongoing health care burden worldwide and is associated with high mortality rates. Sodium-glucose cotransporter-2 inhibitors have consistently shown benefits in cardiovascular and renal outcomes. The effects of sodium-glucose cotransporter-2 inhibitors in acute illness have not been properly investigated. Methods: DEFENDER is an investigator-initiated, multicenter, randomized, open-label trial designed to evaluate the efficacy and safety of dapagliflozin in 500 adult participants with acute organ dysfunction who are hospitalized in the intensive care unit. Eligible participants will be randomized 1:1 to receive dapagliflozin 10mg plus standard of care for up to 14 days or standard of care alone. The primary outcome is a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and intensive care unit length of stay, up to 28 days. Safety will be strictly monitored throughout the study. Conclusion: DEFENDER is the first study designed to investigate the use of a sodium-glucose cotransporter-2 inhibitor in general intensive care unit patients with acute organ dysfunction. It will provide relevant information on the use of drugs of this promising class in critically ill patients. ClinicalTrials.gov registry: NCT05558098
RESUMO Antecedentes: A doença crítica é um importante ônus permanente da assistência médica em todo o mundo e está associada a altas taxas de mortalidade. Os inibidores do cotransportador de sódio-glicose do tipo 2 têm demonstrado consistentemente benefícios nos desfechos cardiovasculares e renais. Os efeitos dos inibidores do cotransportador de sódio-glicose do tipo 2 em doenças agudas ainda não foram devidamente investigados. Métodos: O DEFENDER é um estudo de iniciativa do investigador, multicêntrico, randomizado, aberto, desenhado para avaliar a eficácia e a segurança da dapagliflozina em 500 participantes adultos com disfunção orgânica aguda hospitalizados na unidade de terapia intensiva. Os participantes aptos serão randomizados 1:1 para receber 10mg de dapagliflozina e o tratamento padrão por até 14 dias ou apenas o tratamento padrão. O desfecho primário é um composto hierárquico de mortalidade hospitalar, início de terapia renal substitutiva e tempo de internação na unidade de terapia intensiva, até 28 dias. O monitoramento da segurança será rigoroso durante todo o estudo. Conclusão: O DEFENDER é o primeiro estudo desenvolvido para investigar o uso de um inibidor do cotransportador de sódio-glicose do tipo 2 em pacientes de unidade de terapia intensiva geral com disfunção orgânica aguda. O estudo fornecerá informações relevantes sobre o uso de medicamentos dessa classe promissora em pacientes críticos. Registro ClincalTrials.gov: NCT05558098
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SUMMARY OBJECTIVE: Glucose transporter-1 is a marker involved in energy transport in cancer cells. It has been shown to be a poor prognostic factor in many cancer types, including breast cancer. However, there is no satisfactory parameter predicting treatment in breast cancer patients receiving neoadjuvant therapy. This study investigated the effect of glucose transporter-1 in predicting the treatment response of patients receiving neoadjuvant therapy. METHODS: In this study, glucose transporter-1 immunohistochemistry was applied to tru-cut biopsy of patients who were diagnosed with breast cancer and received neoadjuvant therapy between 2010 and 2021. A built-in scoring system was used to evaluate both the pattern and intensity of glucose transporter-1 immunohistochemistry staining. The relationship between glucose transporter-1 immunohistochemistry staining and other clinicopathological parameters was examined. In addition, the relationship of glucose transporter-1 with response to treatment was investigated. RESULTS: A relationship was found between high glucose transporter-1 expression and other clinicopathological parameters (such as estrogen and progesterone receptor negativity, high Ki-67, triple-negative, and Her2 status). Cases with high glucose transporter-1 expression had either a complete or a partial pathologic response. The result was statistically significant. CONCLUSION: Glucose transporter-1 has the potential to be a biomarker that can be evaluated more objectively as an alternative to Ki-67 labeling index in evaluating the response to treatment in patients receiving neoadjuvant therapy.
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El síndrome de deficiencia del transportador de glucosa tipo 1 es una enfermedad de causa genética, que involucra el gen SLC2A1. En general, se presenta durante los primeros años de vida con retraso en la adquisición de pautas madurativas, epilepsia farmacorresistente y desórdenes del movimiento. La clínica y la disminución de glucosa en líquido cefalorraquídeo permiten sospechar el diagnóstico, el cual debe ser confirmado mediante el estudio molecular del gen SLC2A1. Debido a que se trata de una enfermedad poco frecuente y de expresión clínica variable, el diagnóstico precoz suele representar un desafío para los equipos de salud. Este es importante, ya que la implementación de la terapia cetogénica logra controlar las manifestaciones clínicas y mejora el pronóstico a largo plazo. Presentamos una revisión sobre el déficit del transportador de glucosa tipo 1, que abarca sus características clínicas, bioquímicas, moleculares y terapéuticas.
Glucose transporter type 1 deficiency with a typical onset is a genetic disorder associated with the SLC2A1 gene. Usually appears during the first years of life with severe developmental delay, drugresistant epilepsy, and movement disorders. Diagnosis is suspected based on clinical manifestations and a low glucose level in cerebrospinal fluid, and should be confirmed by the molecular genetic study of the SLC2A1 gene. As it is a rare disease with variable clinical expression, early diagnosis is often challenging for the healthcare team. Nevertheless, this is important because early implementation of ketogenic therapy will lead to control of the clinical manifestations and a better long-term prognosis. Here we review the glucose transporter type 1 deficiency syndrome focusing on its clinical, biochemical, molecular, and therapeutic characteristics.
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Humanos , Errores Innatos del Metabolismo de los Carbohidratos/diagnóstico , Errores Innatos del Metabolismo de los Carbohidratos/genética , Errores Innatos del Metabolismo de los Carbohidratos/terapia , Proteínas de Transporte de Monosacáridos/genética , Epilepsia/diagnóstico , Epilepsia/genética , MutaciónRESUMEN
ObjectiveTo explore the underlying mechanism of bran-fried Atractylodis Rhizoma （AR） in improving gastrointestinal function by comparing the effects of raw AR and bran-fried AR on the small intestine tissue structure and transport-related protein carriers in rats with spleen deficiency syndrome. MethodSeventy male SD rats were randomly divided into a normal group， a model group， high- and low-dose raw AR groups （10， 2.5 g·kg-1）， high- and low-dose bran-fried AR groups （10， 2.5 g·kg-1）， and a compound glutamine group （9 mg·kg-1）， with 10 rats in each group. Except for the normal group， the other six groups were subjected to the spleen deficiency model induced by the method of bitter and cold breaking stagnated Qi and abnormal hunger and fullness for 21 days. After modeling， each treatment group was given medication orally according to the corresponding doses every day for a total of 14 days， and the normal group and the model group were given an equal volume of normal saline orally. During the treatment period， the general survival status， macroscopic syndrome score， daily increase in body weight and food intake， and rectal temperature of the spleen deficiency rats were evaluated， and after the treatment， the rats were sacrificed. The pathological changes in the small intestine tissues of each group were observed by hematoxylin-eosin （HE） staining. The content of serum 5-hydroxytryptamine （5-HT） was detected by enzyme-linked immunosorbent assay （ELISA）， and the content of serum D-xylose， lactate， and amylase was detected by colorimetry. The levels of free fatty acid receptor 3 （FFA3） and peptide transporter 1 （PepT1） in small intestinal tissues were detected by the Bradford method， and the protein expression of sodium-dependent glucose transporter 1 （SGLT1） and glucose transporter 1 （GLUT1） in small intestinal tissue was detected by immunohistochemistry. Real-time fluorescence-based quantitative PCR was used to detect the mRNA expression of glucose transporter 2 （GLUT2）， sodium/hydrogen exchanger 3 （NHE3）， and 5-hydroxytryptamine receptor 4 （5-HT4R）. ResultCompared with the normal group， the model group exhibited symptoms of spleen deficiency， such as sluggishness， squint， reduced food intake， and lethargy at the end of modelling， damaged basic structure of the small intestinal mucosal epithelium and lamina propria， increased serum lactate and 5-HT content， and decreased serum amylase and D-xylose （P<0.01）. Compared with the model group， all treatment groups showed varying degrees of improvement， with the small intestinal microstructure repaired to different degrees. The daily weight gain， anal temperature， and macroscopic syndrome score of spleen deficiency improved to varying degrees （P<0.05， P<0.01）. The serum lactate and 5-HT content decreased to varying degrees， while the serum amylase and D-xylose content increased to varying degrees （P<0.05， P<0.01）. The PepT1 content in the small intestinal tissues increased， while the FFA3 content decreased to varying degrees. The protein expression of SGLT1 and GLUT1 increased， while the mRNA expression of GLUT2 and NHE3 increased to varying degrees. The mRNA expression of 5-HT4R decreased to varying degrees （P<0.05， P<0.01）. Compared with the high- and low-dose raw AR groups， the high- and low-dose bran-fried AR groups showed significant improvement in general conditions and histopathological improvement of the small intestinal tissues. The daily weight gain， anal temperature， and macroscopic syndrome score of spleen deficiency also improved （P<0.05， P<0.01）. The serum lactate and 5-HT content decreased， while the serum amylase and D-xylose content increased （P<0.05， P<0.01）. The PepT1 content in the small intestinal tissues increased， while the FFA3 content decreased. The protein expression of SGLT1 and GLUT1 increased， while the mRNA expression of GLUT2 and NHE3 increased. The mRNA expression of 5-HT4R decreased significantly （P<0.05， P<0.01）. ConclusionBran-fried AR can improve the spleen deficiency-related symptoms and histopathology of the small intestinal tissues in spleen deficiency model rats. Its mechanism may be related to the regulation of the expression of various transport-related protein carriers and the secretion of various digestive enzymes after stir-frying of AR， thus restoring the absorption and transport function of the small intestine.
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Glucose transporter 1(GLUT1)overexpression in tumor cells is a potential target for drug therapy,but few studies have reported screening GLUT1 inhibitors from natural or synthetic compounds.With cur-rent analysis techniques,it is difficult to accurately monitor the GLUT1 inhibitory effect of drug molecules in real-time.We developed a cell membrane-based glucose sensor(CMGS)that integrated a hydrogel electrode with tumor cell membranes to monitor GLUT1 transmembrane transport and screen for GLUT1 inhibitors in traditional Chinese medicines(TCMs).CMGS is compatible with cell membranes of various origins,including different types of tumors and cell lines with GLUT1 expression knocked down by small interfering RNA or small molecules.Based on CMGS continuous monitoring technique,we inves-tigated the glucose transport kinetics of cell membranes with varying levels of GLUT1 expression.We used CMGS to determine the GLUT1-inhibitory effects of drug monomers with similar structures from Scutellaria baicalensis and catechins families.Results were consistent with those of the cellular glucose uptake test and molecular-docking simulation.CMGS could accurately screen drug molecules in TCMs that inhibit GLUT1,providing a new strategy for studying transmembrane protein-receptor interactions.
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Sodium-dependent glucose transporter 2 inhibitors(SGLT2i)are a new class of glucose-lowering drugs, can reduce blood sugar by inhibiting the reabsorption of glucose at the proximal tubule and are widely used in clinical treatment of type 2 diabetes.SGLT2i can not only lower blood sugar, but also offer multiple cardiovascular benefits.Several large randomized controlled trials have confirmed the safety and efficacy of SGLT2i for heart failure with preserved ejection fraction(HFpEF). Herein, we present an overview on advances in SGLT2i for HFpEF.
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Objective:To determine the expression of glucose transporter 3 (GLUT3) in cutaneous squamous cell carcinoma (cSCC), and to evaluate its effect on the cSCC cell line A431.Methods:From June 2016 to December 2020, 22 paraffin-embedded tissue specimens were collected from patients with pathologically confirmed cSCC in the Department of Dermatology, Peking University Third Hospital, and 20 discarded normal skin tissues after dermatological surgeries served as controls. Immunohistochemical assay was performed to determine the GLUT3 expression in cSCC tissues and normal skin tissues. Cultured A431 cells were divided into two groups: GLUT3 overexpression group transfected with a lentiviral vector carrying the SLC2A3 gene, and negative control group transfected with an empty lentiviral vector. Real-time fluorescence-based quantitative PCR and Western blot analysis were conducted to determine the mRNA and protein expression of GLUT3 in A431 cells in different groups, the cell proliferation assay (MTS assay) was performed to estimate the cell proliferative activity, and the live-cell analysis system Incucyte S3 was used for real-time evaluation of the migratory and invasive abilities of A431 cells in different groups. The relative glucose consumption and lactic acid production in A431 cells at 48 hours were measured by using glucose and lactic acid assay kits, retrospectively. Two independent samples t-test was used for comparisons between two groups, and one-way analysis of variance was used for comparisons among multiple groups. Results:The GLUT3 expression was significantly higher in the cSCC tissues than in the normal skin tissues (immunohistochemical assay score: 9.39 ± 2.56 points vs. 2.30 ± 2.60 points; t = 8.91, P < 0.05). Compared with the negative control group, the mRNA and protein expression of GLUT3 markedly increased in the GLUT3 overexpression group. MTS assay showed significantly increased proliferative activity of A431 cells in the GLUT3 overexpression group compared with the negative control group after 24- and 96-hour treatment ( t = 2.49, 3.54, P = 0.048, 0.012, respectively); cell fusion rates in the scratched area were significantly higher in the GLUT3 overexpression group than in the negative control group in the cell migration assay at 6, 12 18, and 24 hours and cell invasion assay at 12, 18, and 24 hours (all P < 0.05). At 48 hours, the relative glucose consumption and lactic acid production in A431 cells were significantly higher in the GLUT3 overexpression group than in the negative control group ( t = 2.98, 2.20, P = 0.011, 0.038, respectively) . Conclusion:GLUT3 was highly expressed in the cSCC tissues, and may participate in the occurrence and development of cSCC by providing energy to cSCC cells via promoting glucose uptake in cells to enhance their proliferative, migratory and invasive abilities.
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Objective To investigate the effect of miR-93-5p on the expression of hepatocyte growth factor(HGF),glucose transporter 4(GLUT4)and distribution of GLUT4 in insulin resistance cell model.Methods The cells were divided into control group,model group,miR-93-5p inhibitor group,inhibitor-NC group,miR-93-5p mimics group and mimics-NC group.The cells in control group were cultured normally,while insulin resistance cell model was constructed in cells of model group.The other groups were transfected with miR-93-5p inhibitor,inhibitor-NC,miR-93-5p mimics and mimics-NC,respectively.And the insulin resistance model was constructed after transfection.Cell viability was detected by CCK-8.The kit was used to measure the glu-cose content in the cell supernatant and the glucose consumption was calculated.The expressions of miR-93-5p,HGF and GLUT4 mRNA were detected by qPCR.The expressions of HGF and GLUT4 protein were detected by Western blotting.The expression and distribution of GLUT4 were detected by immunofluorescence.Results Compared with the control group,the cell survival rate,glucose consumption,HGF,GLUT4 mRNA and protein expression levels were significantly decreased(all P＜0.01),miR-93-5p level was significantly increased(P＜0.01),and GLUT4 membrane distribution was decreased in the model group.Compared with the model group,the cell survival rate,glucose consumption,HGF,GLUT4 mRNA and protein expres-sion levels were significantly increased(all P＜0.05),miR-93-5p level was significantly decreased(P＜0.01),and GLUT4 mem-brane distribution was increased in the miR-93-5p inhibitor group.The results were opposite in the miR-93-5p mimics group.Conclusion miR-93-5p can inhibit the expression of HGF and GLUT4 and reduce the membrane distribution of GLUT4 in insulin resistance cell model,which can promote insulin resistance.
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Objective:To explore the effect of long noncoding RNA(lncRNA)THAP7-AS1 on the glycolysis of gastric cancer(GC)cells by regulating methyltransferase-like 3(METTL3)mediated N6-methyladenosine(m6A)modification. Methods:Gene Expression Profiling Interactive Analysis(GEPIA)database was used to analyze the expression levels of THAP7-AS1 and METTL3 in GC tissues and their relationship with the overall survival of GC patients.Real-time fluorescence quantitative PCR and Western blotting were used to analyze the expression of THAP7-AS1,METTL3 mRNA,glucose transporter 1(GLUT1)mRNA,and METTL3 protein in GC tissues and paracancerous tissues samples collected from 80 GC patients in Department of Oncology,The Third Affiliated Hospital of Zunyi Medical University(the First People's Hospital of Zunyi),and the relationship between THAP7-AS1 levels and the clinicopathological characteristics of GC patients was analyzed.Real-time fluorescence quantitative PCR and Western blotting were used to verify the expression of THAP7-AS1,METTL3 mRNA,GLUT1 mRNA,and METTL3 protein in GES-1,BGC-823 and SGC-7901 cells.Lentiviral infection was used to knock-down THAP7-AS1 or overexpress METTL3 BGC-823 and SGC-7901 cells,and real-time fluorescence quantitative PCR and Western blotting were used to examine effect of different treatment on the expression of THAP7-AS1,METTL3 mRNA,GLUT1 mRNA,and METTL3 protein;colorimetry assay was used to detect the m6A modification level in the total RNA;methylated RNA immunoprecipitation(MeRIP)-quantitative PCR(qPCR)was used to detect the GLUT1 m6A modification level;glycolysis stress test kits were used to detect the extracellular acidification rate(ECAR),glucose uptake and lactate production of treated GC cells;Western blotting was used to examine the expression levels of METTL3,GLUT1,M2 type pyruvate kinase(PKM2)and lactic dehydrogenase(LDHA)proteins in treated GC cells;EdU staining,wound healing assay and Transwell invasion assay were used to evaluate the proliferation,migration and invasion of treated GC cells.Finally,a mouse model of subcutaneously transplanted GC tumor was established using nude mice,and the effect of knocking-down THAP7-AS1 was assessed by measuring the tumor volume and weight,as well as the expression levels of METTL3 and GLUT1 proteins in transplanted GC tumor tissues. Results:Analysis of the GEPIA database showed that the expression levels of THAP7-AS1 and METTL3 was higher in GC tissue than those in normal gastric tissues,and the expression levels of THAP7-AS1 and METTL3 are negatively correlated with overall survival of GC patients(P＜0.05).Compared with the paracancerous tissues(or normal gastric epithelial cells),the expression levels of THAP7-AS1,METTL3 mRNA,GLUT1 mRNA and METTL3 protein was significantly increased in GC tissues(or GC cells),and the higher the expression of THAP7-AS1,the higher the TNM stage,the lower the degree of tumor differentiation,and the easier the occurrence of microvascular infiltration and lymph node metastasis(P＜0.05).Knocking-down of THAP7-AS1 down-regulated the expression levels of METTL3 mRNA,GLUT1 mRNA and METTL3 protein,the m6A modification levels in total RNA and GLUT1,the ECAR levels,the glucose uptake,the lactate production,EdU positive rate,scratch healing rate,the number of invaded cells,and the expression levels of glycolysis-related proteins(METTL3,GLUT1,PKM2 and LDHA)in GC cells(P＜0.05).Overexpression of METTL3 could partially reverse these effects of THAP7-AS1 knock-down(P＜0.05).In vivo experiments showed that THAP7-AS1 knock-down can obviously inhibit the growth of transplanted GC tumors(P＜0.05). Conclusion:lncRNA THAP7-AS1 can promote the glycolysis which further promotes the proliferation,migration and invasion of GC cells by regulating METTL3 mediated m6A modification.
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Glucose transporters (GLUTs) encoded by the solute carrier family 2 (SLC2) gene belong to the major facilitator superfamily (MFS) and are responsible for the transmembrane transport of glucose in the body. As the earliest discovered member of the GLUTs, glucose transporter 1 (GLUT1) is mainly found in the blood-brain barrier and erythrocyte membrane, and plays an important role in maintaining stable blood glucose concentration and energy supply to the brain. The transmembrane transport capacity of GLUT1 is not only related to the gene expression of SLC2 A1 on the cellular membrane, but also to the transport kinetic regulation of GLUT1. Generally, SLC2 A1 expression is regulated at the transcriptional, post-transcriptional, translational and post-translational levels, and the transport kinetics regulation includes a series of GLUT1 inhibitors, such as intramembrane glycan-binding site inhibitor, extramembrane glycan-binding site inhibitor, adenosine-binding effect inhibitors and the highly selective inhibitor BAY-876. SLC2 A1 gene deletions and mutations can cause embryonic mortality and GLUT1 deficiency syndrome. In contrast, abnormally high SLC2 A1 expression is associated with various diabetic complications (e. g. diabetic retinopathy and diabetic nephropathy), neurocognitive impairment and tumorigenesis. In this paper, the structure, function, expression and activity regulation of GLUT1 and its relationship with diseases were reviewed to provide a reference for the GLUT1-related clinical research and drug development.