Sodium-glucose cotranspor ter 2 (SGLT2) inhibitors in nephrolithiasis: should we "gliflozin" patients with kidney stone disease? / Inibidores de cotransportadores sódio-glicose-2 (SGLT2) na nefrolitíase - devemos "gliflozinar" os litiásicos?

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?

Control metabólico de pacientes diabéticos tipo 2 tratados con empagliflozina: serie de casos / Metabolic control in type 2 diabetic patients treated with empagliflozin: A case series

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.

Dapagliflozin in patients with critical illness: rationale and design of the DEFENDER study / Dapagliflozina em pacientes com doença crítica: justificativa e desenho do estudo DEFENDER

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

Predicting response to neoadjuvant therapy with glucose transporter-1 in breast cancer

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.

Deficiencia del transportador de glucosa tipo 1: aspectos clínicos, diagnóstico y terapéutica / Glucose transporter type 1 deficiency syndrome: clinical aspects, diagnosis, and treatment

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.

Tumor cell membrane-coated continuous electrochemical sensor for GLUT1 inhibitor screening / 药物分析学报

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.

Expression of glucose transporter 3 in cutaneous squamous cell carcinoma and its effect on the proliferation, invasion and migration of A431 cells / 中华皮肤科杂志

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.

Research progress on the role and mechanisms of action of sodium-dependent glucose transporter 2 inhibitors in heart failure with preserved ejection fraction / 中华老年医学杂志

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.

Effect of Raw and Bran-fried Atractylodis Rhizoma on Protein Carriers Related to Small Intestinal Absorption Transport in Spleen Deficiency Rats / 中国实验方剂学杂志

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.

Research progress on T cell glycolytic metabolism in oral lichen planus / 口腔疾病防治

@#Oral lichen planus (OLP) is a chronic inflammatory disease of the oral mucosa. The pathogenesis of OLP is still unclear. Immune abnormalities mediated by T cells and related cytokines play a crucial role in the pathogenesis of OLP. In recent years, glycolytic metabolism-related transporters, enzymes and regulators, such as glucose transporter-1 (Glut1), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), lactate dehydrogenase A (LDHA), mammalian target of rapamycin (mTOR) and hypoxia inducible factor-1α (HIF-1a), have attracted an increasing amount of attention in OLP by regulating the proliferation and differentiation of T cells and the secretion of inflammatory factors. It has been shown that 2-deoxy-D-glucose (2-DG) or rapamycin (RAPA) inhibits the glycolytic metabolism of T cells and then inhibits OLP. This article reviews the research progress of glycolytic metabolism-related transporters, enzymes and regulatory factors in OLP in recent years.

Los inhibidores SGLT2: una mirada al futuro del tratamiento de la insuficiencia cardiaca / Sodium-glucose cotransporter 2 inhibitors for the management of heart failure

Heart failure (HF) is a global health problem. There is a strong association h between HF and type 2 diabetes mellitus (DM2), with an increasing prevalence of patients having both conditions concomitantly. Sodium-glucose cotransporter 2 inhibitors (ISGLT2) significantly reduce cardiovascular events, including cardiovascular death. In this article we will focus on the current evidence about the effectiveness of these medications in adults with heart failure with reduced or preserved ejection fraction.

Effects of sodium-glucose cotransporter-2 inhibitors on nutritional status in heart failure with reduced ejection fraction

SUMMARY OBJECTIVE: This study aimed to evaluate the effects of sodium-glucose cotransporter-2 inhibitors on nutritional status in patients with heart failure with reduced ejection fraction. METHODS: The sodium-glucose cotransporter-2 inhibitor treatment was initiated in 153 patients with heart failure with reduced ejection fraction who were symptomatic despite optimal medical treatment and were followed up for 6 months. The Minnesota Living With Heart Failure Questionnaire scores, New York Heart Association functional class, NT-pro-BNP levels, and nutritional index scores of the patients were evaluated before sodium-glucose cotransporter-2 inhibitor treatment and at the 6-month follow-up. The nutritional status of the patients was evaluated with the COntrolling NUTritional Status score, Geriatric Nutritional Risk Index, and Prognostic Nutritional Index. RESULTS: After sodium-glucose cotransporter-2 inhibitor treatment, significant changes were observed in the mean scores of the three different nutritional indexes: COntrolling NUTritional Status (before: 2.76±2.43 vs. after: 1.12±1.23, p<0.001), Geriatric Nutritional Risk Index (before: 98.2±9.63 vs. after: 104.4±5.83, p<0.001), and Prognostic Nutritional Index (before: 37.9±4.63 vs. after: 42.9±3.83, p<0.001) scores. A significant decrease in the number of patients with malnutrition was observed according to the COntrolling NUTritional Status (before: 46.4% vs. after: 9.7%, p<0.001), Geriatric Nutritional Risk Index (before: 41.8% vs. after: 18.9%, p=0.006), and Prognostic Nutritional Index (before: 36.6% vs. after: 13.7%, p=0.007) scores. A significant functional improvement was observed in patients after sodium-glucose cotransporter-2 treatment: Minnesota Living With Heart Failure Questionnaire scores (before: 39.2±7.2 vs. after: 20.4±7.4, p<0.001), NT-pro-BNP levels (before: 2989±681 vs. after: 1236±760, p<0.001), and New York Heart Association class (before: class II-III: 95.5%; class IV: 4.5% vs. after: class II-III: 78%; class IV: 0%, p<0.001). CONCLUSION: In patients with heart failure with reduced ejection fraction who are symptomatic despite optimal medical treatment, the addition of an sodium-glucose cotransporter-2 inhibitor to treatment can significantly improve both the nutritional and functional statuses.

Hemidistonía y hemicorea en un paciente pediátrico con déficit del transportador de glucosa de tipo 1 / Hemidystonia and hemichorea in a pediatric patient with glucose transporter type 1 deficiency

El síndrome de deficiencia del transportador de glucosa cerebral de tipo 1 es una enfermedad neurometabólica rara en pediatría. Existe un fenotípico clásico (85 %) y otro no clásico (15 %). Ambos fenotipos se asocian con hipoglucorraquia. Se identifican múltiples mutaciones en el gen SLC2A1. El tratamiento es la terapia cetogénica. Se presenta un varón que comenzó a los cuatro años con hemicorea y hemidistonía medicado con anticonvulsivantes sin respuesta clínica, por lo que consultó nuevamente a los seis años. Con sospecha diagnóstica de síndrome de déficit de glut-1 atípico se realizó punción lumbar; el diagnóstico se confirmó por la presencia de hipoglucorraquia. Inmediatamente después de iniciar la dieta cetogénica, el paciente no presentó más movimientos anormales durante los siguientes 8 años hasta la actualidad, ya cumplidos los 14 años.

Glucose transporter type 1 deficiency syndrome is a rare pediatric neurometabolic disorder. There are two phenotypes: the classical phenotype (85%) and the non-classic (15%). Both phenotypes are associated with hypoglycorrhachia. Multiple mutations are described in the SCL2A1 gene. The treatment is the ketogenic diet. We report a case of a four-year-old male patient who started with hemichorea and hemidystonia and was medicated with drugs for seizures without clinical response, that's why his parents made another pediatric consultation at his six-year-old. With the suggestive clinical findings of glucose transporter type 1 deficiency syndrome the lumbar puncture was made confirming the diagnosis. Immediately after starting the ketogenic diet the patient stopped making abnormal movements up to the moment when he is fourteen years old, eight years after.

The diagnostic value of glucose transporter 1 level of erythrocyte membrane and glucose uptake rate of erythrocytes in glucose transporter type 1 deficiency syndrome / 中华实用儿科临床杂志

Objective:To explore new methods to assist the diagnosis of glucose transporter type 1 deficiency syndrome (GLUT1-DS).Methods:Sixteen children with epilepsy and/or movement disorder carrying the SLC2A1 mutation who admitted to Department of Pediatrics, the First Medical Center, Chinese People′s Liberation Army General Hospital and Department of Nutrition, Shanghai Deji Hospital from October 2019 to October 2020 were retrospectively analyzed.GLUT1-DS was diagnosed based on clinical phenotype, glucose level in CSF and/or genetic testing results.Forty-four healthy children who underwent physical examination in the First Medical Center, Chinese People′s Liberation Army General Hospital during the same period were selected as healthy control group.Glucose transporter 1 (GLUT1) level on the membrane surface of peripheral red blood cells and erythrocyte glucose uptake rate were measured by flow cytometry and glucose oxidase method, respectively.Their differences between groups were compared by the rank sum test.The receiver operating cha-racteristic (ROC) curve was plotted to assess their diagnostic value. Results:Sixteen children were diagnosed as GLUT1-DS.GLUT1 levels of 16 children with GLUT1-DS were significantly lower than those of healthy control group [17.96% (13.43%, 22.12%) vs.27.93% (24.76%, 34.30%), Z=5.249, P<0.001]. Area under curve (AUC) was 0.946, and weighted Kappa was 0.791 ( P<0.001). The erythrocyte glucose uptake was measured in 12 children with GLUT1-DS, which was significantly lower than that of healthy control group [23.14% (14.80%, 26.45%) vs.27.40% (24.61%, 32.82%), Z=2.366, P=0.018]. AUC and weighted Kappa were 0.724 and 0.344, respectively ( P<0.001), showing a poor consistency. Conclusions:GLUT1 level on the surface of human erythrocyte membrane measured by flow cytometry may be a new method to assist the diagnosis of GLUT1-DS.The erythrocyte glucose uptake rate test requires stricter experimental conditions and needs further investigation.

PXR activation impairs hepatic glucose metabolism partly via inhibiting the HNF4α-GLUT2 pathway

Drug-induced hyperglycemia/diabetes is a global issue. Some drugs induce hyperglycemia by activating the pregnane X receptor (PXR), but the mechanism is unclear. Here, we report that PXR activation induces hyperglycemia by impairing hepatic glucose metabolism due to inhibition of the hepatocyte nuclear factor 4-alpha (HNF4α)‒glucose transporter 2 (GLUT2) pathway. The PXR agonists atorvastatin and rifampicin significantly downregulated GLUT2 and HNF4α expression, and impaired glucose uptake and utilization in HepG2 cells. Overexpression of PXR downregulated GLUT2 and HNF4α expression, while silencing PXR upregulated HNF4α and GLUT2 expression. Silencing HNF4α decreased GLUT2 expression, while overexpressing HNF4α increased GLUT2 expression and glucose uptake. Silencing PXR or overexpressing HNF4α reversed the atorvastatin-induced decrease in GLUT2 expression and glucose uptake. In human primary hepatocytes, atorvastatin downregulated GLUT2 and HNF4α mRNA expression, which could be attenuated by silencing PXR. Silencing HNF4α downregulated GLUT2 mRNA expression. These findings were reproduced with mouse primary hepatocytes. Hnf4α plasmid increased Slc2a2 promoter activity. Hnf4α silencing or pregnenolone-16α-carbonitrile (PCN) suppressed the Slc2a2 promoter activity by decreasing HNF4α recruitment to the Slc2a2 promoter. Liver-specific Hnf4α deletion and PCN impaired glucose tolerance and hepatic glucose uptake, and decreased the expression of hepatic HNF4α and GLUT2. In conclusion, PXR activation impaired hepatic glucose metabolism partly by inhibiting the HNF4α‒GLUT2 pathway. These results highlight the molecular mechanisms by which PXR activators induce hyperglycemia/diabetes.

Effects of resveratrol on the activity of infantile hemangioma-derived endothelial cells / 中华皮肤科杂志

Objective:To investigate the effect of the glucose transporter 1 (Glut-1) inhibitor resveratrol on the activity of infantile hemangioma (IH) -derived endothelial cells (HemEC) .Methods:IH tissues were collected from 4 cases of proliferating IH and 4 cases of involuting IH, and immunohistochemical study was performed to determine the Glut-1 expression. Primary HemEC were extracted from 4 proliferating IH tissues, real-time fluorescence-based quantitative PCR (qPCR) and Western blot analysis were performed to determine the mRNA and protein expression of Glut-1 in HemEC and human umbilical vein endothelial cells (HUVEC) , respectively. HemEC were cultured in vitro and treated with 0 (control group) , 50, 100, 200, 400 and 800 μmol/L resveratrol for 24 hours, respectively. Cell counting kit-8 (CCK8) assay was performed to evaluate the proliferative ability of HemEC in the above groups, and the 50% inhibitory concentration (IC50) was calculated. The migratory ability and apoptosis level of HemEC were assessed by Transwell assay and flow cytometry, respectively. Intergroup comparisons were performed using t test or analysis of variance, and multiple comparisons were performed using least significant difference- t test. Results:Immunohistochemical study showed that Glut-1 was expressed in vascular endothelial cells derived from both proliferating and involuting IH tissues, and the Glut-1 expression was abundant in the proliferating IH but markedly decreased in the involuting IH tissues. The mRNA and protein expression levels of Glut-1 were significantly higher in HemEC (1.793 ± 0.041, 1.959 ± 0.144, respectively) than in HUVEC (0.820 ± 0.073, 0.648 ± 0.046, t = 16.35, 12.28, respectively, both P < 0.001) . After the treatment with Glut-1 inhibitor resveratrol at different concentrations, the proliferative ability of HemEC significantly differed among the control group, 50-, 100-, 200-, 400- and 800-μmol/L resveratrol groups ( F = 1 043.00, P < 0.001) , and was significantly lower in all the resveratrol groups than in the control group (all P < 0.05) . The IC50 of resveratrol was calculated to be 150 μmol/L by using GraphPad Prism 8 software. Transwell assay and flow cytometry showed significantly decreased number of migratory HemEC but significantly increased apoptosis rate respectively in the 150 μmol/L resveratrol group (61 ± 5, 13.01% ± 0.45%, respectively) compared with the control group (150 ± 6, 3.93% ± 0.68%, t = 15.11, 19.34, respectively, both P < 0.001) . Conclusion:The key glycolytic enzyme Glut-1 was highly expressed in proliferating IH tissues and HemEC, and resveratrol could inhibit the proliferation and migration of HemEC, but promote their apoptosis.

Effect of different glucose concentrations on the uptake of 18F-FDG in non-small cell lung cancer / 中华核医学与分子影像杂志

Objective:To explore the effect of different glucose concentrations on the uptake of 18F-FDG and the expression of glucose transport protein(Glut)-1 and Glut-3 in non-small cell lung cancer (NSCLC). Methods:NSCLC cell line A549 cells were cultured in DMEM medium with glucose concentrations of 3.9, 5.0, 6.1, 8.3 and 11.1 mmol/L respectively for 24 h. Then 3.7×10 4 Bq 18F-FDG was added into each group and γ counter was used to measure the radioactivity count 1 h later. Western blot was used to examine the expression of Glut-1 and Glut-3. One-way analysis of variance and Bonferroni test were used for data analysis. The correlation was analyzed by Pearson correlation analysis. Results:The 18F-FDG uptake rates in 3.9, 5.0, 6.1, 8.3 and 11.1 mmol/L groups were (4.89±0.83)%, (4.07±0.23)%, (3.66±0.29)%, (3.34±0.16)% and (3.29±0.24)%, respectively ( F=7.05, P=0.006). Compared with 3.9 mmol/L group, the 18F-FDG uptake rates in 8.3 and 11.1 mmol/L groups were reduced and differences were statistically significant ( P values: 0.013, 0.010), while there were no statistical differences between the other groups ( P values: 0.057-0.999). The relative expressions of Glut-1 and Glut-3 in each group were 1.17±0.10, 1.00±0.00, 0.84±0.07, 0.70±0.18, 0.61±0.16, and 1.14±0.05, 1.00±0.00, 0.86±0.12, 0.71±0.05, 0.40±0.06, respectively ( F values: 10.26 and 51.94, P values: 0.001, <0.001). Moreover, the 18F-FDG uptake rates were positively correlated with the expression of Glut-1 and Glut-3 ( r values: 0.775 and 0.744, both P=0.001). Conclusions:When the glucose concentration fluctuates within 3.9-11.1 mmol/L, the change of glucose will affect the 18F-FDG uptake rate and the expression of Glut-1 and Glut-3 in A549 cells. Moreover, the 18F-FDG uptake rate is related to the expressions of Glut-1 and Glut-3.

HIF / 中南大学学报(医学版)

OBJECTIVES@#To analyze the expressions and distributions of hypoxia-inducible factor-1α (HIF-1α), CD147, and glucose transporter 1 (GLUT1) in epidermis from psoriasis vulgaris and normal people, and to explore the associations among these proteins and their roles in hypoxic HaCaT cell line.@*METHODS@#The expression levels of HIF-1α, CD147, and GLUT1 were determined by immunohistochemistry staining in skin biopsies from 48 psoriasis vularis patients and 33 healthy subjects. Cobalt chloride (CoCl@*RESULTS@#HIF-1α, CD147, and GLUT1 were highly expressed and the glycolytic capacity was increased in lesions of psoriasis vulgaris; HIF-1α upregulated the expression of CD147 and GLUT1, increased the lactate production and decreased the ATP level in CoCl@*CONCLUSIONS@#Glycolytic capacity increases in the injured keratinocytes of psoriasis vulgaris, suggesting that HIF-1α, CD147, and GLUT1 are associated with glycolysis, which can be considered as the promising targets for psoriasis therapy.

Molecular mechanism of geniposide in regulating GLUT2 glycosylation in pancreatic β cells / 中国中药杂志

Type 2 diabetes mellitus( T2 DM) is a common chronic metabolic disease characterized by persistent hyperglycemia and insulin resistance. In pancreatic β-cells,glucose-stimulated insulin secretion( GSIS) plays a pivotal role in maintaining the balance of blood glucose level. Previous studies have shown that geniposide,one of the active components of Gardenia jasminoides,could quickly regulate the absorption and metabolism of glucose,and affect glucose-stimulated insulin secretion in pancreatic β cells,but the specific mechanism needs to be further explored. Emerging evidence indicated that glycosylation of glucose transporter( GLUT) has played a key role in sensing cell microenvironmental changes and regulating glucose homeostasis in eucaryotic cells. In this study,we studied the effects of geniposide on the key molecules of GLUT2 glycosylation in pancreatic β cells. The results showed that geniposide could significantly up-regulate the mRNA and protein levels of Glc NAc T-Ⅳa glycosyltransferase( Gn T-Ⅳa) and galectin-9 but had no signi-ficant effect on the expression of clathrin,and geniposide could distinctively regulate the protein level of Gn T-Ⅳa in a short time( 1 h) under the conditions of low and medium glucose concentrations,but had no significant effect on the protein level of galectin-9. In addition,geniposide could also remarkably affect the protein level of glycosylated GLUT2 in a short-time treatment. The above results suggested that geniposide could quickly regulate the protein level of Gn T-Ⅳa,a key molecule of protein glycosylation in INS-1 rat pancreatic βcells and affect the glycosylation of GLUT2. These findings suggested that the regulation of geniposide on glucose absorption,metabolism and glucose-stimulated insulin secretion might be associated with its efficacy in regulating GLUT2 glycosylation and affecting its distribution on the cell membrane and cytoplasm in pancreatic β cells.

Progress in the clinical application and correlation between glucose transporter-1 and / 生物医学工程学杂志

Because of the unobvious early symptoms and low 5-year survival rate, the early diagnosis and treatment is of great significance for patients with non-small cell lung cancer. Glucose transporter-1 is the most widely distributed glucose transporters in various tissue cells in the human body, whose expression in non-small cell lung cancer is closely related to the histological types, lymph node metastasis, degree of differentiation, progression and prognosis.