Glucose Transporter Protein Research Articles (Page 1)

Background/Objectives: Obesity and hyperglycemia predispose patients to respiratory infections. Although the lung is a major organ to utilize glucose, pulmonary glucose homeostasis in type 2 diabetic (T2Dx) subjects remains poorly characterized. We hypothesized that pulmonary glucose transport would be altered during T2Dx, which would be rescued with long-term metformin treatment. Methods: T2Dx was induced by feeding mice a high-fat diet for 16 weeks, with metformin treatment administered during the final 8 weeks. Results: Glucose transporter (GLUT) protein expression and trafficking was quantified by Western blotting and the biotinylated photolabeling assay, respectively. T2Dx mice exhibited obesity, and increased glucose levels in blood and bronchoalveolar lavage (BAL) fluid. T2Dx also significantly decreased protein expression of GLUTs from Class I (i.e., GLUT-2 and -4) and class III (i.e., GLUT-10 and -12) isoforms in lung. Metformin treatment restored the protein expression of GLUT-2, -4, and -10, but not GLUT-12. Pulmonary cell surface expression of GLUT-4 and -8 was also significantly reduced in T2Dx mice and rescued by metformin. Conclusions: These findings suggest that alterations in pulmonary GLUT expression and trafficking during diabetes could contribute to the elevated airway glucose levels and severity of respiratory infections. Metformin treatment restored pulmonary glucose transport during T2Dx.

Purpose: To determine whether perinatal taurine supplementation enhances glucose transporter-4 (GLUT4) expression in the skeletal muscle of adult male offspring of rats born to diabetic mothers. Methods: Female Wistar rats (n = 9) were maintained under standard laboratory conditions with free access to food and water. Diabetes was induced in six rats via a single intraperitoneal injection of streptozotocin (50 mg/kg), followed by 20 % glucose supplementation for 24 hours. The remaining three rats served as non-diabetic controls. After diabetes confirmation, all females were mated with healthy males (3:1 ratio). From conception to weaning, pregnant rats received either 3 % taurine in drinking water (n = 16) or plain tap water (n = 16), resulting in four groups: Non-DM (n = 8), non-DM + T (n = 8), DM (n = 8), and DM + T (n = 8). Following weaning, only male offspring in each group (n = 8) were selected and maintained on a standard diet and water. At 16 weeks of age, fasting blood glucose, plasma insulin, lipid profiles, and skeletal muscle GLUT4 protein expression were assessed. Results: Male offspring of diabetic mothers exhibited significantly elevated fasting glucose and triglyceride levels and reduced insulin levels compared to non-diabetic controls (non-DM; p < 0.05). Perinatal taurine supplementation in diabetic dams significantly reduced triglyceride levels, increased plasma insulin, and enhanced GLUT4 expression in offspring skeletal muscle compared to non-diabetic (non-DM; p < 0.05) and diabetic groups (DM; p < 0.05). Conclusion: Perinatal taurine supplementation may mitigate metabolic disturbances in the offspring of female diabetic rats by improving insulin levels, reducing triglycerides, and upregulating GLUT4 expression in skeletal muscle.

Background & Objectives: Data on the efficacy and adverse effects of finerenone in patients with nondiabetic chronic kidney disease (CKD) are limited, particularly regarding ethnic diversity. This study aimed to evaluate the outcomes of finerenone in patients with nondiabetic CKD previously treated with standard therapies and investigate associated adverse effects, including hyperkalemia and hypotension. Methods: This is a retrospective exploratory study. It is a single-center study including patients with nondiabetic CKD who visited King Fahad Medical City in Riyadh, Saudi Arabia. The primary exposure was finerenone treatment, assessing its effects on albuminuria, kidney function, and blood pressure (BP), following prior use of renin–angiotensin–aldosterone system and sodium–glucose transport protein 2 inhibitors. The measured outcomes were the urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). The UACR (primary endpoint) was calculated as the mean of two morning spot urine samples collected consecutively 1 day apart. During each 4-week treatment period, secondary endpoints included changes in UACR, as determined by a 24 h urine sample, BP, and eGFR. The Wilcoxon signed-rank test was used to compare changes in continuous variables before and after therapy initiation. Statistical significance was set at p < 0.05. Results: This study included 16 patients with nondiabetic CKD (median age, 38.5 years [range, 35–50 years]; 56.3% male). The baseline eGFR was 66 mL/min/1.73 m2 (47–82.5), with a UACR of 90.0 mg/g (58.8–132.5). No hyperkalemia was observed (potassium level, 4 mmol/L [3.8–4.4]). However, significant reductions in systolic and diastolic BPs were observed. Albuminuria improved significantly: the UACR decreased from 90.0 to 39.3 mg/g (p = 0.04). No adverse events, including hyperkalemia or hypotension, were reported. Conclusions: Finerenone showed promise in reducing albuminuria and blood pressure among patients with nondiabetic chronic kidney disease, with no significant adverse effects reported. These findings suggest potential benefits for this patient population, warranting further investigation.

Cobalt exposure increases fasting plasma glucose by inhibiting hepatic glycogen synthesis and enhancing gluconeogenesis.

Objective: To explore the role and mechanism of the hypoxia-inducible factor-1 (HIF-1) pathway in rat retinal precursor R28 cell injury caused by the OPTN (E50K) mutation. Methods: This experimental study was conducted from November 2023 to October 2024. The retinas of 18-month-old wild-type (WT) mice and normal tension glaucoma mice with the OPTN (E50K) mutation were extracted for proteomic analysis. In vitro models carrying the genes of green fluorescent protein (GFP), GFP-OPTN (WT) and GFP-OPTN (E50K) were constructed by transfecting R28 cells with adeno-associated viruses. Western blotting and PCR were used to detect the protein and mRNA expressions of apoptotic index B-lymphocytoma-2-associated X protein (BAX), HIF-1α, and energy metabolism enzymes including glucose transporter 1 (GLUT1) and lactate dehydrogenase A (LDHA). R28 cells were treated with the HIF-1α inhibitor Lificiguat at concentrations of 0, 25, 50, 75 and 100 μmol/L for 12, 24 and 48 hours, respectively. According to the cell counting kit-8 detection results, 75 μmol/L Lificiguat was selected to treat the cells for 24 hours. The protein and mRNA expression changes of HIF-1α, GLUT1, LDHA and BAX were detected after the addition of Lificiguat. The statistical analysis was performed using the one-way analysis of variance and Tukey test. Results: There were 1 564 differentially expressed proteins in the retinas of mice in the experimental group compared with those in the control group, and these were significantly enriched in the HIF-1 signaling pathway. The protein expression levels of BAX, HIF-1α, GLUT1 and LDHA in OPTN (E50K) mutant R28 cells were 1.28±0.15, 1.54±0.21, 1.28±0.15 and 1.20±0.16, respectively. They were significantly increased compared with those in R28 cells transfected with the GFP-OPTN (WT) gene (0.96±0.04, 0.87±0.07, 0.90±0.10, 0.87±0.02; all P<0.05). The mRNA expression levels of BAX, HIF-1α, GLUT1 and LDHA in OPTN (E50K) mutant R28 cells were 1.20±0.06, 2.89±0.21, 2.37±0.22 and 1.27±0.22, respectively. They were also significantly increased compared with those in R28 cells transfected with the GFP-OPTN (WT) gene (0.87±0.14, 0.88±0.23, 1.24±0.18, 0.94±0.07; all P<0.05). The protein expression levels of HIF-1α, LDHA and BAX in OPTN (E50K) mutant R28 cells treated with Lificiguat were 0.62±0.11, 0.65±0.15 and 0.76±0.03, respectively. They were significantly decreased compared with those in OPTN (E50K) mutant R28 cells untreated with Lificiguat (0.88±0.04, 0.92±0.04, 1.08±0.07; all P<0.05). The mRNA expression levels of HIF-1α, LDHA and BAX in OPTN (E50K) mutant R28 cells treated with Lificiguat were 1.06±0.06, 1.11±0.14 and 1.01±0.01, respectively. They were also significantly decreased compared with those in OPTN (E50K) mutant R28 cells untreated with Lificiguat (1.34±0.09, 1.45±0.14, 1.12±0.00; all P<0.05). The protein expression levels of GLUT1 in OPTN (E50K) mutant R28 cells without and with Lificiguat were 0.99±0.10 and 1.09±0.01, while the mRNA expression levels were 1.23±0.06 and 1.31±0.13, respectively. The expression of the GLUT1 protein and mRNA in OPTN (E50K) mutant R28 cells slightly increased after treatment with Lificiguat, and there was no statistically significant difference (all P>0.05). Conclusions: The OPTN (E50K) mutation affects the expression of energy metabolism enzymes GLUT1 and LDHA in R28 cells by regulating the HIF-1 pathway, inducing apoptosis of R28 cells. Lificiguat can effectively inhibit the overexpression of HIF-1α caused by the OPTN (E50K) mutation and protect R28 cells.

Cancer cells relyheavily on glycolysis for energy production andsurvival. Therefore, targeting glycolysis represents a promising therapeuticapproach to cancer treatment. This study investigates the anticancerpotential of myrrhanone B (MN) and myrrhanol B (ML), two bioactivetriterpenoids isolated from the ethyl acetate extract of Commiphora mukul (CMEE), with a particular focuson their effects on cancer metabolism and apoptosis. The cytotoxiceffects of CMEE, MN, and ML were evaluated in MCF-7 and MDA-MB-231breast cancer cell lines by using MTT assays. Molecular docking andmolecular dynamics (MD) simulations were performed to examine interactionswith glucose transporter-1 (GLUT1). Glucose uptake and lactate productionwere assessed calorimetrically to determine their impact on glycolysis.Apoptosis was analyzed using flow cytometry with annexin V/PI staining,while reactive oxygen species (ROS) levels and caspase-3 activitywere measured to explore oxidative stress and apoptotic pathways.CMEE, MN, and ML significantly reduced cell viability in a dose-dependentmanner, with IC50 values at 48 h of 30 μg/mL forCMEE, 18 μM for MN, and 23 μM for ML in MDA-MB-231 cellsand 40 μg/mL for CMEE, 22 μM for MN, and 27 μM forML in MCF-7 cells. In vitro, glucose uptake and lactatelevels were significantly reduced in MDA-MB-231 and MCF-7 cells followingtreatment with IC50 concentrations of MN, ML, and CMEE,suggesting a strong antiglycolytic effect. In silico docking and simulation predict good complementarity of MN and MLwith GLUT1 protein and high binding affinity for the GLUT1 receptor,which may be a probable drug target for these compounds. Furthermore,apoptosis assays revealed a significant increase in early and lateapoptotic cell populations following treatment with IC50 doses of CMEE, MN, and ML, which correlate with the elevated intracellularROS levels and enhanced caspase-3 activity. CMEE and its bioactivecompounds, MN and ML, exert potent anticancer effects by glycolysissuppression, elevating ROS levels, and promoting apoptosis in MDA-MB-231and MCF-7 breast cancer cells.

The liver and gut play a central role in modulating bile acid metabolism. Our recent study found that supplementation with sodium butyrate (NaB) from microbiota might slow diabetes progression and ameliorate liver function in diabetic mice. The role of NaB in the homeostasis of mitochondrial energy metabolism and bile acid metabolism needs to be investigated further, so this study was conducted by us. We used an ELISA kit to detect biochemical indicators related to mice; HE and PAS were used to stain and analyze tissues; CCK8 was used to detect cell viability; and WB was used to detect related indicators. We found here that NaB administration enormously reduced liver hypertrophy and steatosis in diabetic mice, improved liver and gut function and the release of inflammatory factors in diabetic mice, and ameliorated mitochondrial function both in vitro and in vivo. NaB incubation significantly increased bile acid metabolism-related receptors under diabetic conditions; the intracellular content of enzymes related to liver function was elevated within liver cells. Glucose transport proteins GLUT2 and NaB receptor GPR43 were upregulated by NaB on the cell membrane. The actuation of the intracellular signaling proteins PI3K, AKT, and GSK3 was inhibited by NaB under diabetic conditions. The present study proved that the microbiota metabolite NaB has positive effects on bile acid metabolic homeostasis by promoting mitochondrial energy metabolism in enterocytes and the liver, and the GPR43-PI3K-AKT-GSK3 signaling pathway should contribute to this effect.

Mammalian cells regulate their glucose levels by redistributing glucose transporter proteins within the cell. Glucose Transporter 4 (GLUT4) is the main insulin-regulated glucose transporter in mammalian cells. Insulin signals the redistribution of GLUT4 from intracellular compartments to the cell surface. The mechanisms of the release of GLUT4 and subsequent transport to the plasma membrane remain an open question. Here, a biologically plausible model of GLUT4 translocation is presented. Using a stochastic queuing model, we find that changing only the number of fusion sites available for GLUT4-containing vesicles as a function of insulin is sufficient to explain experimental observations. Thus, the activity of the fusion sites could be the primary determinant of the dynamics of GLUT4.

To explore the effects of combined exposure to atmospheric PM_(2.5) and a high-fat and high-sugar diet on glucose metabolism and learning and memory abilities in rats. Thirty-two 3-week-old SPF-grade Wistar rats, half male and half female, were randomly divided into four groups: the control group, the PM_(2.5) group, the high-fat and high-sugar group, and the high-fat and high-sugar + PM_(2.5) group, with 8 rats in each group. The control group and the PM_(2.5) group were fed with normal maintenance feed(total energy 14.23 kJ/g), while the high-fat and high-sugar group and the high-fat and high-sugar + PM_(2.5) group were fed with high-fat and high-sugar feed(total energy 19.80 kJ/g). The control group and the high-fat and high-sugar group were raised in a clean room for 24 weeks. After 16 weeks of raising, the high-fat and high-sugar group and the high-fat and high-sugar + PM_(2.5) group were exposed to PM_(2.5) using an online PM_(2.5) concentration and small animal whole-body exposure system. The PM_(2.5) exposure concentration was 8 times the real-time outdoor PM_(2.5) concentration, for 6 hours per day, 5 days per week, for a total of 8 weeks. The concentration during the exposure period was 177.20(48.53, 358.01) μg/m~3. The body weight of the rats was measured every 2 weeks. After 24 weeks of the experiment, the Morris water maze test was conducted to evaluate learning and memory abilities. The oral glucose tolerance test(OGTT) was used to calculate the area under the curve(AUC). The fasting blood glucose(FBG), fasting serum insulin(FINS), and glycosylated hemoglobin(HbA1c) levels of the rats were detected. The homeostasis model assessment for insulin resistance index(HOMA-IR) was calculated. The expression levels of glucose transporter 4(GLUT4) and phosphatidylinositol3-ki-nase(PI3K)/protein kinase B(AKT) signaling pathway-related proteins in the hippocampus of the rats were detected by Western blot. The body weight of rats increased with the duration of exposure, but there was no statistically significant difference in body weight among the four groups at the same time point(P &gt; 0.05). Compared with the control group(14.81±1.22) and the PM_(2.5) group(14.24±0.84), the AUC of the high-fat high-sugar group(16.26±0.86) and the high-fat high-sugar + PM_(2.5) group(16.44±1.99) was significantly increased, with statistical significance(P&lt;0.05). Compared with the control group, the levels of FBG, FINS, HbA1c and HOMA-IR in the PM_(2.5) group, the high-fat high-sugar group and the high-fat high-sugar + PM_(2.5) group were significantly increased(P&lt;0.05). Compared with the PM_(2.5) group and the high-fat high-sugar group, the levels of FBG, FINS, HbA1c and HOMA-IR in the high-fat high-sugar + PM_(2.5) group were significantly increased(P&lt;0.05). The escape latency of the high-fat high-sugar group and the high-fat high-sugar + PM_(2.5) group was(11.11±2.69) s and(14.80±5.25) s, respectively, which was significantly higher than that of the control group(7.25±2.79) s(P&lt;0.05). The number of times rats crossed the platform in the PM_(2.5) group, the high-fat high-sugar group and the high-fat high-sugar + PM_(2.5) group was(4.38±1.19) times, (5.00±1.31) times and(3.38±1.69) times, respectively, which was significantly lower than that of the control group(8.25±1.67) times(P&lt;0.05), and the high-fat high-sugar + PM_(2.5) group(3.38±1.69) times was lower than the high-fat high-sugar group(5.00±1.31) times(P&lt;0.05). Compared with the control group, the expression of GLUT4, insulin receptor(IR), IRS1, P-PI3K and P-AKT proteins in the hippocampus of the rats in the PM_(2.5) group, the high-fat high-sugar group and the high-fat high-sugar + PM_(2.5) group was down-regulated(P&lt;0.05). Compared with the PM_(2.5) group, the expression of GLUT4, IR, IRS1 and P-PI3K proteins in the hippocampus of the rats in the high-fat high-sugar group and the high-fat high-sugar + PM_(2.5) group was down-regulated. Spearman correlation analysis showed that FBG, FINS, HbA1c and HOMA-IR were negatively correlated with the number of times rats crossed the platform(P&lt;0.05), and AUC, HbA1c and FINS were positively correlated with the escape latency(P&lt;0.05). The expression levels of proteins related to the IR/PI3K/AKT signaling pathway were positively correlated with the number of times rats crossed the platform(P&lt;0.05). Exposure to PM_(2.5) and a high-fat high-sugar diet can cause abnormal glucose metabolism and learning and memory impairment in rats, and the combined exposure of both further exacerbated these changes.

Dextran-engineered Cu-MOF nanozyme with multi-enzyme mimetic cascade for cuproptosis-enhanced synergistic therapy in triple-negative breast cancer.

The aim of this study was to describe changes in estimated glomerular filtration rate (eGFR), left ventricular ejection fraction (LVEF) and clinical outcomes in a real-world cohort of patients with heart failure with reduced ejection fraction (HFrEF) and atrial fibrillation (AF). A total of 321 patients (67 [58–74] years old, 19.3% females) were included; 134 (41.7%) had AF. AF patients were less frequently prescribed angiotensin receptor–neprilysin inhibitor (ARNi), with no differences concerning sodium–glucose transport protein 2 inhibitors (SGLT2is) and had lower median baseline eGFR values. At 6- and 12-month follow-ups, renal function declined similarly in both groups, with no difference in the proportion of patients experiencing an eGFR decrease of ≥30% from baseline. Regarding cardiac remodeling, patients without AF showed a higher proportion of individuals with an LVEF improvement of ≥10% from baseline, however with no differences between groups in LVEF final recovery. During a median follow-up of 582 (339–1481) days, AF patients showed a higher risk of composite outcome (aHR, 95% CI: 2.12, 1.16–3.86) and of hospitalization for heart failure (hHF) (2.80, 1.44–5.46), without differences in all-cause death. Delta eGFR changes with at least a 30% decline in eGFR were associated with a higher risk of the primary endpoint. Despite lower baseline renal function, AF patients exhibited similar LVEF improvement and renal decline, which emphasizes the importance of guideline-directed medical therapy. AF was associated with a higher risk of adverse events, primarily driven by hHF.

Studies utilizing cell-based systems to investigate plant-based diets for diabetes management are gaining attention due to the adverse effects associated with commercially available drugs. However, the molecular mechanisms underlying the anti-diabetic effects of specific plant-derived products remain inadequately explored. The major aim of our study was to elucidate the molecular mechanisms by which bioactive compounds in the fruit of Solanum spp. influence key proteins associated with type 2 diabetes. The expressions of genes such as glucose transporter protein 4 (GLUT4), myocyte enhancer factor-2 (MEF-2A), and nuclear respiratory factor-1 (NRF-1) were investigated in a palmitate-induced C2C12 cell model of type 2 diabetes mellitus. The structures of these proteins were retrieved from the protein database, while bioactive compounds previously identified in Solanum spp. were obtained from PubChem site. Drug-likeness properties of these compounds (ligands) were assessed. The docked protein-ligand complexes were further analyzed using the Protein-Ligand Profiler web server. Our results showed that the studied compounds from Solanum spp. profoundly upregulated GLUT4 expression (9–19-fold increase) in the C2C12 cell line, thus surpassing the effects of the standard anti-diabetic drug metformin. Additionally, activities of antioxidant enzymes catalase, superoxide dismutase, and glutathione peroxidase were elevated. Molecular docking showed that rutin, an abundant flavonoid from Solanum spp., had the highest binding affinity for the active sites of the target proteins. These findings provide new mechanistic insight into the anti-diabetic effects of Solanum spp., primarily due to its high rutin content, which plays a major role in the plant’s glucose-regulating and antioxidant actions. Our findings underscore the potential use of Solanum spp. as an affordable functional food for managing type 2 diabetes, especially in developing countries with limited resources for purchasing drugs. Although promising, our findings should be further validated by clinical studies.

From the perspective of circular RNA forkhead box protein O3(circFOXO3) regulating glycolysis in osteoarthritis(OA) chondrocytes, this study investigated the mechanism by which Tougu Xiaotong Capsules(TGXTC) alleviated OA degeneration. In in vivo experiments, after randomized grouping and relevant interventions, morphological staining was used to observe structural changes in cartilage tissue. The mRNA level of circFOXO3 in cartilage tissue was detected by real-time quantitative PCR(RT-qPCR). Western blot analysis was used to detect changes in the expression of glucose transporter 1(GLUT1), hexokinase 2(HK2), pyruvate kinase M2(PKM2), lactate dehydrogenase A(LDHA), and matrix metalloproteinase 13(MMP13). In in vitro experiments, fluorescence in situ hybridization(FISH) was used to detect circFOXO3 expression in chondrocytes from each group. A lentiviral vector was used to construct circFOXO3-silenced(sh-circFOXO3) chondrocytes. RT-qPCR was used to analyze the changes in circFOXO3 levels after silencing, and Western blot was used to assess the regulatory effects of TGXTC on GLUT1, HK2, PKM2, LDHA, and MMP13 proteins in interleukin-1β(IL-1β)-induced chondrocytes under sh-circFOXO3 conditions. Masson staining and alcian blue staining results showed that the cartilage layer structure in the TGXTC and positive drug groups was improved compared with that in the model group. The mRNA level of circFOXO3 was significantly upregulated in both the TGXTC and positive drug groups, while the expression of the above-mentioned proteins was significantly reduced. FISH results showed that TGXTC upregulated the fluorescence intensity of circFOXO3 in IL-1β-induced chondrocytes. In the circFOXO3 silencing experiment, compared with the IL-1β group, circFOXO3 levels in the IL-1β + sh-circFOXO3 group were significantly decreased. Compared with the IL-1β + TGXTC group, circFOXO3 levels were significantly reduced in the IL-1β + sh-circFOXO3 + TGXTC group. Western blot results indicated that the elevated levels of GLUT1, HK2, PKM2, LDHA, and MMP13 proteins in chondrocytes of the IL-1β group were significantly inhibited by TGXTC intervention. However, this regulatory effect was attenuated after circFOXO3 silencing. In conclusion, TGXTC alleviate glycolytic metabolism disorder in OA chondrocytes and delay OA degeneration by regulating circFOXO3.

Background/Objectives: Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) function as effectors in the Hippo pathway and have attracted attention due to their association with tumor formation. Glucose transporter (GLUT) proteins also contribute to the proliferation of cancer cells. In this study, we investigated the effect of YAP/TAZ on GLUT1 expression in endometrial carcinoma, as well as the clinical relevance and prognostic value of YAP/TAZ. Methods: The effects of YAP and TAZ knockdown and YAP overexpression on GLUT1 expression in human endometrial carcinoma-derived HHUA and Ishikawa cells were evaluated using RT-qPCR. In addition, we performed immunohistochemical expression of 100 tissue samples of diagnosed endometrial carcinoma. Based on staining intensity and the percentage of positively stained tumor cells, the immunoreactivity score was calculated, which ranged from 0 to 12. Results: YAP/TAZ were identified as important factors in the regulation of GLUT1 expression in HHUA and Ishikawa cells. In addition, a significant correlation (progression-free survival p < 0.05) was observed between TAZ and GLUT1 expression in tissues from endometrial carcinoma patients, and nuclear expression of TAZ was associated with poor prognosis (p < 0.05). Conclusions: YAP/TAZ promote tumor growth via GLUT1. Therapeutic targeting of YAP/TAZ could therefore be useful in the development of future treatments.

Targeted drug delivery seeks to revolutionize disease treatment by enhancing therapeutic efficacy and specificity. However, developing and achieving precisely targeted delivery remains a significant challenge, particularly in cancers such as triple-negative breast cancer (TNBC), which lack traditional markers for targeted delivery. TNBC cells overexpress glucose transport proteins (GLUTs) on their surfaces, providing an opportunity for targeting. Herein, sugar-based ionic liquids (Glyco-ILs or GILs) are developed and used to modify poly (lactic-co-glycolic acid) (PLGA) nanocarriers (NPs), show enhanced affinity and selectivity towards TNBC cells and human and mouse erythrocytes. Inhibition assays, molecular docking simulations, and liquid chromatography-mass spectrometry (LCMS) analysis data show that the enhanced nanoparticle affinity for TNBC cells is likely due to a combination of specific binding interactions with GLUT transporters and endocytosis. The observed RBC affinity is evidenced to be driven by interactions with RBC membrane GLUTs along with their unique serum protein corona on the nanoparticle surface. In vivo, experiments in a healthy BALB/c mouse model show that Glyco-IL-NPs demonstrate longer retention time in the bloodstream and a significant reduction in liver accumulation relative to the control. These findings suggest that Glyco-IL-modified PLGA nanoparticles (GIL-NPs) hold a promising approach for selective drug delivery, particularly in cells that overexpress GLUTs.

Early intervention for infantile hemangioma (IH) typically involves the use of the first-line drug propranolol, which can be taken orally or applied topically. However, approximately 10% of patients develop resistance, highlighting the need to elucidate the underlying molecular mechanisms. This study found that the expression of glucose transporter 1 (GLUT1) was significantly increased in IH tissues. Knockdown of GLUT1 significantly inhibited the cell viability, colony formation, and angiogenesis of HemEC cells. Moreover, high GLUT1 levels caused insensitivity to propranolol treatment in IH as HemEC cells showed few significant changes to intracellular GLUT1 protein expression and glycolysis level upon treatment with propranolol, while overexpression of GLUT1 promoted colony formation and increased the IC50 value of HemEC cells with propranolol treatment. The YT521-B homology domain family protein 1 (YTHDF1), an m6A reader in mRNA, was significantly increased in IH tissues compared with normal adjacent tissues. MeRIP-qPCR results showed that YTHDF1 binds to GLUT1 mRNA and promoted its stability and translation efficiency, resulting in GLUT1 upregulation, thereby inhibiting the sensitivity of IH to propranolol. Additionally, YTHDF1 overexpression promoted the ability of colony formation and increased the IC50 value of HemEC cells with propranolol treatment. However, this promotion was reversed by knockdown of GLUT1. Collectively, our results demonstrated that YTHDF1-mediated m6A recognition of GLUT1 is vital in IH development and propranolol insensitivity. The YTHDF1/GLUT1 axis may serve as a potential target for inhibiting IH progression from aggravating and overcoming propranolol resistance in IH.

Abstract Ferroptosis is an emerging therapeutic strategy in pancreatic cancer (PC) therapy. However, existing ferroptosis often concentrate on the generation of lipid peroxide (LPO), ignoring the negative feedback from intracellular anomalous metabolism, such as lactic acid accumulation. Herein, an “AND” logic gate functional nanoreactor is constructed with a combination of curcumin and glucose oxidase (Gox) (NRs@Cur@Gox) for metabolic remodeling‐mediated starvation, ferroptosis, and immunotherapy. In acidic tumor cells, NRs@Cur@Gox is specifically activated to improve the permeability of the membranes, resulting in increased hydrogen peroxide (H2O2) production via the catalysis of Gox. High H2O2 subsequently induces self‐destruction of the nanoreactor, releasing Cur and quinone methides to inhibit the expression of glucose transporter protein 1, generate lactate and deplete glutathione (GSH), respectively. Exhausted intracellular glucose and blockage of extracellular glucose transport interdict tumor cells from the root. Moreover, decreased lactate, increased H2O2, and GSH depletion synergistically activate ferroptosis. Starvation therapy combined with ferroptosis induces significant immunogenic cell death (ICD), promotes cytotoxic T lymphocyte proliferation, and inhibit PC regression. Importantly, the decreased lactate in the tumor microenvironment reverses immunosuppressive tumors into “hot” tumors, reinforcing the immunotherapeutic efficiency of NRs@Cur@Gox. Overall, this study provides a versatile metabolic intervention strategy for PC‐ferroptosis immunotherapy.

Infantile hemangioma is the most common anomalies affecting young children. This disease occurs in 2—9% of newborns. Before laser therapy and the discovery of propranolol’s properties, sclerotherapy, close-focus X-ray therapy, and other crippling, low-efficacy methods were widespread. After their use, patients needed additional reconstructive surgical treatment and psychological help. This article presents a clinical case of the treatment of patient K., 6 years old, who underwent a single close-focus radiotherapy at the age of 9 months. The aesthetic result of the intervention was unsatisfactory, and treatment with propranolol was contraindicated due to somatic complications. Doppler ultrasound, transcutaneous oxygenometry, and formation thermometry were used for diagnosis. At the age of 3, a child underwent interstitial coagulation of hyperplastic vessels using a laser with a wavelength of 970 nm. At the age of 5.5 years, the second stage of treatment was performed — surgical removal of a residual hemangioma with scarred tissues. Histological examination showed increased expression of glucose transporter protein GLUT1 in the vascular wall, which is typical for infantile hemangioma. Six months after the end of treatment, a normotrophic, mild postoperative scar was observed, the anatomy of the upper lip was restored, the lip was soft and elastic.

To investigate the effects of glut polymorphisms on 18Fluorine-fluorodeoxyglucose (18F-FDG) uptake rates. The 18F-FDG positron emission tomography/computed tomography images and mass lesion metabolism standard uptake value maximum (SUVmax) results of the patients were evaluated. Glucose transporter protein-1 (GLUT-1)-XbaI G>T (rs2754218) and HaeIII T>C (rs1385129) polymorphisms and their effects on 18F-FDG uptake rates were investigated using DNA obtained from peripheral blood. When the Xbal G>T genotype distribution of the patients was examined, the Xbal G/G genotype was found to be 87%, the Xbal G/T genotype 12%. The XbaI T/T phenotype was detected in only one patient (1%). In the HaeIII T>C genotype distribution, the HaeIII C/C genotype was found as 54%, the HaeIII T/C genotype as 31%, and the HaeIII T/T genotype as 15%. When the Xbal and HaeIII genotypes were examined together, the number of polymorphic genotypes was significantly higher in the lung and bronchial tumor groups compared to other cancer types. The presence of polymorphism in at least one of the two gene regions, in the lung-bronchial tumor group and the high SUVmax value in this patient group, may indicate a change in the involvement rates.

Bioactive peptides PIISVYWK and FSVVPSPK improve glucose homeostasis by targeting DPP-IV and glucose transport in type 2 diabetic mice.