Regulation Of Glucose Transport Research Articles

Lactobacillus casei-fermented Amomum xanthioides ameliorates metabolic dysfunction in high-fat diet-induced obese mice.

Amomum xanthioides (AX) has been used as an edible herbal medicine to treat digestive system disorders in Asia. Additionally, Lactobacillus casei is a well-known probiotic commonly used in fermentation processes as a starter. The current study aimed to investigate the potential of Lactobacillus casei-fermented Amomum xanthioides (LAX) in alleviating metabolic disorders induced by high-fat diet (HFD) in a mouse model. LAX significantly reduced the body and fat weight, outperforming AX, yet without suppressing appetite. LAX also markedly ameliorated excessive lipid accumulation and reduced inflammatory cytokine (IL-6) levels in serum superior to AX in association with UCP1 activation and adiponectin elevation. Furthermore, LAX noticeably improved the levels of fasting blood glucose, serum insulin, and HOMA-IR through positive regulation of glucose transporters (GLUT2, GLUT4), and insulin receptor gene expression. In conclusion, the fermentation of AX demonstrates a pronounced mitigation of overnutrition-induced metabolic dysfunction, including hyperlipidemia, hyperglycemia, hyperinsulinemia, and obesity, compared to non-fermented AX. Consequently, we proposed that the fermentation of AX holds promise as a potential candidate for effectively ameliorating metabolic disorders.

Synaptotagmins family affect glucose transport in retinal pigment epithelial cells through their ubiquitination-mediated degradation and glucose transporter-1 regulation.

Synaptotagmins (SYTs) are a family of 17 membrane transporters that function as calcium ion sensors during the release of Ca2+-dependent neurotransmitters and hormones. However, few studies have reported whether members of the SYT family play a role in glucose uptake in diabetic retinopathy (DR) through Ca2+/glucose transporter-1 (GLUT1) and the possible regulatory mechanism of SYTs. To elucidate the role of the SYT family in the regulation of glucose transport in retinal pigment epithelial cells and explore its potential as a therapeutic target for the clinical management of DR. DR was induced by streptozotocin in C57BL/6J mice and by high glucose medium in human retinal pigment epithelial cells (ARPE-19). Bioinformatics analysis, reverse transcriptase-polymerase chain reaction, Western blot, flow cytometry, ELISA, HE staining, and TUNEL staining were used for analysis. Six differentially expressed proteins (SYT2, SYT3, SYT4, SYT7, SYT11, and SYT13) were found between the DR and control groups, and SYT4 was highly expressed. Hyperglycemia induces SYT4 overexpression, manipulates Ca2+ influx to induce GLUT1 fusion with the plasma membrane, promotes abnormal expression of the glucose transporter GLUT1 and excessive glucose uptake, induces ARPE-19 cell apoptosis, and promotes DR progression. Parkin deficiency inhibits the proteasomal degradation of SYT4 in DR, resulting in SYT4 accumulation and enhanced GLUT1 fusion with the plasma membrane, and these effects were blocked by oe-Parkin treatment. Moreover, dysregulation of the myelin transcription factor 1 (Myt1)-induced transcription of SYT4 in DR further activated the SYT4-mediated stimulus-secretion coupling process, and this process was inhibited in the oe-MYT1-treated group. Our study reveals the key role of SYT4 in regulating glucose transport in retinal pigment epithelial cells during the pathogenesis of DR and the underlying mechanism and suggests potential therapeutic targets for clinical DR.

Development of Aptamer-DNAzyme based metal-nucleic acid frameworks for gastric cancer therapy.

The metal-nucleic acid nanocomposites, first termed metal-nucleic acid frameworks (MNFs) in this work, show extraordinary potential as functional nanomaterials. However, thus far, realized MNFs face limitations including harsh synthesis conditions, instability, and non-targeting. Herein, we discover that longer oligonucleotides can enhance the synthesis efficiency and stability of MNFs by increasing oligonucleotide folding and entanglement probabilities during the reaction. Besides, longer oligonucleotides provide upgraded metal ions binding conditions, facilitating MNFs to load macromolecular protein drugs at room temperature. Furthermore, longer oligonucleotides facilitate functional expansion of nucleotide sequences, enabling disease-targeted MNFs. As a proof-of-concept, we build an interferon regulatory factor-1(IRF-1) loaded Ca2+/(aptamer-deoxyribozyme) MNF to target regulate glucose transporter (GLUT-1) expression in human epidermal growth factor receptor-2 (HER-2) positive gastric cancer cells. This MNF nanodevice disrupts GSH/ROS homeostasis, suppresses DNA repair, and augments ROS-mediated DNA damage therapy, with tumor inhibition rate up to 90%. Our work signifies a significant advancement towards an era of universal MNF application.

Purification and characterization of 3-O-methyl-D-glucose from the seed coat of Vigna mungo (L.) Hepper

Vigna mungo. L (Black gram) belonging to the Leguminosae family is a most abundant source of protein for human and animal diets. Over 8.5 million tonnes of black gram are being produced worldwide, and after confiscating the endosperm for the protein source, the seed coat is dumped as agro-waste and used as feed for the cattle. This study aims to investigate and profile the metabolites in three distinct parts of V. mungo seeds: coat, cotyledon, and intact seed. Also, it has been hypothesized that sugar methylation plays a pivotal role in facilitating black gram seed germination by serving as an energy source during metabolic processes. In our study, A total of forty-nine compounds belonging to the class such as fatty acids, saccharides, triterpenes, sterols, and vitamins were detected in various parts of V. mungo seed by gas chromatography-mass spectrometry (GC-MS). Most interestingly, 3-O-methyl-D-glucose (3-OMG) was commonly detected in methanolic extract of coat, intact seed, and cotyledon with peak area percentages of 3.076, 1.157, and 1.100 %, respectively. Based on the highest peak area percentage in the coat, this compound was purified by using a silica gel column with a mesh size of 60–120 followed by Biotage SNAP cartridge KP-C18-HS (12 g). The yield and purity of the purified fractions were found to be 11.78 & 94.19 %, respectively by high-performance liquid chromatography (HPLC) analysis. Further, the mass confirmation of purified fraction containing 3-OMG (m/z - 217.06 g/mol) was done by liquid chromatography-mass spectrometry (LC-MS/MS) and reconfirmed with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS). The MS/MS analysis of the fragment showed m/z 206.91 for 3-OMG which corresponds to the association of the sodium adduct. The concentration of 3-OMG was quantified as 332.65 µg/g of dry weight in the coat of V. mungo by HPLC analysis. Also, among the antioxidant assays conducted, such as DPPH, ABTS, FRAP, and NOS, it was observed that the methanolic extract of coat exhibited the most significant antioxidant activity. The 3-OMG is commonly used as a non-metabolized analogue of glucose by regulating glucose transporter, especially GLUT-4 that regulates the absorption of glucose by insulin into muscle and fat cells. This study supports the black gram seed with coat as an alternative medicine to regulate blood glucose.

Depletion of TBC1D4 improves the metabolic exercise response by overcoming genetically induced peripheral insulin resistance.

The RabGTPase-activating protein (RabGAP) TBC1D4 (=AS160) represents a key component in the regulation of glucose transport into skeletal muscle and white adipose tissue (WAT) and is therefore crucial during the development of insulin resistance and type-2 diabetes. Increased daily activity has been shown to be associated with improved postprandial hyperglycemia in allele carriers of a loss-of-function variant in the human TBC1D4 gene. Using conventional Tbc1d4-deficient mice (D4KO) fed a high-fat diet (HFD), we show that already a moderate endurance exercise training leads to substantially improved glucose and insulin tolerance and enhanced expression levels of markers for mitochondrial activity and browning in WAT from D4KO animals. Importantly, in vivo and ex vivo analyses of glucose uptake revealed increased glucose clearance in interscapular brown adipose tissue (iBAT) and WAT from trained D4KO mice. Thus, chronic exercise is able to overcome the genetically induced insulin resistance caused by the Tbc1d4-depletion. Gene variants in TBC1D4 may be relevant in future precision medicine as determinants of exercise response.

Dietary phytochemicals as regulators of gut inflammation in the context of type 2 diabetes

Numerous disorders, including type 2 diabetes and even COVID-19, are linked to poor gut health and inflammation(1,2). In addition to impacting food digestion and absorption, gut inflammation worsens diabetes outcomes by causing gut microbial dysbiosis, disrupting tight junctions (allowing microbial metabolites to freely enter into circulation), and altering glucose absorption(3). ACE2 is a crucial regulator of gut health and has received much attention during the COVID-19 pandemic due to its role as a major viral entry protease. Studies have shown that the ACE2/Ang-(1-7)/Mas axis is important in managing inflammation and maintaining normal glucose metabolism(3). Dietary phytochemicals are plant bioactive compounds, with promising anti-inflammatory and anti-diabetic properties, and may affect these processes. In this work, we aimed to look at the link between inflammation, ACE2 and the glucose transporters, SGLT1 and GLUT2, and how phytochemicals could be used to normalise the changes brought about by inflammation in Caco-2/TC7 human intestinal epithelium cells. We first examined how gut inflammation, ACE2 and glucose transporters are related and proceeded to look at the effect of some chosen phytochemicals on regulating glucose transport via modulation of the ACE2/Ang(1-7)/Mas axis. This included genistein (an isoflavone from soyabeans), sulforaphane (an isothiocyanate found in Brassica, especially broccoli), apigenin (a flavone found in vegetables and herbs), and artemisinin (a sesquiterpene lactone used as a drug). The impact of phytochemicals on the SARS-CoV-2 viral entry receptors, ACE2 and TMPRSS2, was also examined as a secondary outcome. To induce inflammation, the Caco2/TC7 cells were co-stimulated with IL-1β (25 ng/mL) and TNF-α (50 ng/mL) for varying durations (24 h, 48 h, 72 h, 168 h) and changes in target gene expression (ACE2, SGLT1, GLUT2, TMPRSS2) were assessed by droplet digital PCR. IL-6 and IL-8 were assessed as markers of inflammation in the cell culture media by multiplex ELISA. Inflammation increased ACE2, TMPRSS2 and SGLT1 mRNA. ACE2 increased with cytokine exposure duration, coupled with an obvious decrease in IL-8, SGLT1 and TMPRSS2. Pearson correlation analysis revealed that the increase in ACE2 was strongly associated with decreases in SGLT1 (r = −0.99, p<0.01) and IL-8 (r = −0.959, p<0.05), implying ACE2 to play a crucial role in gut inflammation and postprandial glycaemia. After establishing the gut cell inflammation model, we compared the effect of the phytochemicals on our target genes in cells cultured in normal and pro-inflammatory environments. None of the tested phytochemicals were effective in reducing IL-8 secretion, while phytochemicals showed varying effects on the target genes. Genistein normalised the effects of inflammation on the target genes with less effect from the other tested phytochemicals. However, further research is required to assess the importance of genistein in vivo in the context of gut inflammation and type 2 diabetes.

Superior glucose metabolism supports NH4+ assimilation in wheat to improve ammonium tolerance.

The use of slow-release fertilizers and seed-fertilizers cause localized high-ammonium (NH4 +) environments in agricultural fields, adversely affecting wheat growth and development and delaying its yield. Thus, it is important to investigate the physiological responses of wheat and its tolerance to NH4 + stress to improve the adaptation of wheat to high NH4 + environments. In this study, the physiological mechanisms of ammonium tolerance in wheat (Triticum aestivum) were investigated in depth by comparative analysis of two cultivars: NH4 +-tolerant Xumai25 and NH4 +-sensitive Yangmai20. Cultivation under hydroponic conditions with high NH4 + (5 mM NH4 +, AN) and nitrate (5 mM NO3 -, NN), as control, provided insights into the nuanced responses of both cultivars. Compared to Yangmai20, Xumai25 displayed a comparatively lesser sensitivity to NH4 + stress, as evident by a less pronounced reduction in dry plant biomass and a milder adverse impact on root morphology. Despite similarities in NH4 + efflux and the expression levels of TaAMT1.1 and TaAMT1.2 between the two cultivars, Xumai25 exhibited higher NH4 + influx, while maintaining a lower free NH4 + concentration in the roots. Furthermore, Xumai25 showed a more pronounced increase in the levels of free amino acids, including asparagine, glutamine, and aspartate, suggesting a superior NH4 + assimilation capacity under NH4 + stress compared to Yangmai20. Additionally, the enhanced transcriptional regulation of vacuolar glucose transporter and glucose metabolism under NH4 + stress in Xumai25 contributed to an enhanced carbon skeleton supply, particularly of 2-oxoglutarate and pyruvate. Taken together, our results demonstrate that the NH4 + tolerance of Xumai25 is intricately linked to enhanced glucose metabolism and optimized glucose transport, which contributes to the robust NH4 + assimilation capacity.

The role of STAT3/VAV3 in glucolipid metabolism during the development of HFD-induced MAFLD.

Metabolic-associated fatty liver disease (MAFLD) is a globally prevalent chronic hepatic disease. Previous studies have indicated that the activation of the signal transducer and activator of transcription3 (STAT3) plays a vital role in MAFLD progression at the very beginning. However, the specific association between STAT3 and abnormal hepatic metabolism remains unclear. In this study, activated inflammation was observed to induce abnormal glucolipid metabolic disorders in the hepatic tissues of high-fat diet (HFD)-fed ApoE-/- mice. Furthermore, we found that the activation of STAT3 induced by HFD might function as a transcriptional factor to suppress the expression of VAV3, which might participate in intracellular glucolipid metabolism and the regulation of glucose transporter 4 (GLUT4) storage vesicle traffic in the development of MAFLD both in vitro and in vivo. We verified that VAV3 deficiency could retard the GLUT4 membrane translocation and impair the glucose homeostasis. Additionally, VAV3 participates in cholesterol metabolism in hepatocytes, eventually resulting in the accumulation of intracellular cholesterol. Moreover, rAAV8-TBG-VAV3 was conducted to restore the expression of VAV3 in HFD-fed ApoE-/- mice. VAV3 overexpression was observed to improve glucose homeostasis as well as attenuate hepatic cholesterol accumulation in vivo. In conclusion, the STAT3/VAV3 signaling pathway might play a significant role in MAFLD by regulating glucose and cholesterol metabolism, and VAV3 might be a potential therapeutic strategy which could consequently ameliorate MAFLD.

PyLKB1 regulates glucose transport via activating PyAMPKα in Yesso Scallop Patinopecten yessoensis under high temperature stress

Liver kinase B1 (LKB1) is a classical serine/threonine protein kinase and plays an important role in maintaining energy homeostasis through phosphorylate AMP-activated protein kinase α subunit (AMPKα). In this study, a homologous molecule of LKB1 with a typical serine/threonine kinase domain and two nuclear localization sequences (NLSs) was identified in Yesso Scallop Patinopecten yessoensis (PyLKB1). The mRNA transcripts of PyLKB1 were found to be expressed in haemocytes and all the examined tissues, including gill, mantle, gonad, adductor muscle and hepatopancreas, with the highest expression level in hepatopancreas. PyLKB1 was mainly located in cytoplasm and nucleus of scallop haemocytes. At 3 h after high temperature stress treatment (25 °C), the mRNA transcripts of PyLKB1, PyAMPKα, and PyGLUT1 in hepatopancreas, the phosphorylation level of PyAMPKα at Thr170 in hepatopancreas, the positive fluorescence signals of PyLKB1 in haemocytes, glucose analogue 2-NBDG content in haemocytes, and glucose content in hepatopancreas, haemocytes and serum all increased significantly (p < 0.05) compared to blank group (15 °C). However, there was no significant difference at the protein level of PyLKB1 and PyAMPKα. After PyLKB1 was knockdown by siRNA, the mRNA expression level of PyGLUT1, and the glucose content in hepatopancreas and serum were significantly down-regulated (p < 0.05) compared with the negative control group receiving an injection of siRNA-NC. However, there were no significant difference in PyGLUT1 expression, glucose content and glucose analogue 2-NBDG content in haemocytes. These results collectively suggested that PyLKB1-PyAMPKα pathway was activated to promote glucose transport by regulating PyGLUT1 in response to high temperature stress. These results would be helpful for understanding the function of PyLKB1-PyAMPKα pathway in regulating glucose metabolism and maintaining energy homeostasis under high temperature stress in scallops.

Glucose Regulates Glucose Transport and Metabolism via mTOR Signaling Pathway in Bovine Placental Trophoblast Cells.

It has been confirmed that improving the energy level of the diet contributed to the greater reproductive performance and birth weight of calves in periparturient dairy cows. To investigate the effect of glucose on nutrient transport during fetal development, the bovine placental trophoblast cells (BPTCs) were cultured in media with different glucose concentrations (1, 2, 4, 8, or 16 mg/mL). Subsequently, the BPTCs were cultured in media with 1, 8 mg/mL glucose and 8 mg/mL glucose plus 100 nmol/L rapamycin (the inhibitor of mTOR pathway). Compared with the 1 mg/mL glucose, the addition of 8 mg/mL glucose stimulated cell proliferation, upregulated the mRNA abundance of the glucose transporter GLUT1 and GLUT4, and increased the activity of glucose metabolism-related enzyme glucose-6-phosphate dehydrogenease (G6PD), lactate dehydrogenase (LDHA) and phosphoglycerate kinase 1 (PGK1), as well as adenosine-triphosphate (ATP) content (p < 0.05).Furthermore, compared with the treatment of 1 mg/mL glucose, adding 8 mg/mL of glucose-upregulated gene expression in the mTOR signaling pathway, including phosphatidylinositol3-kinase (PI3K), protein kinase B (Akt), mammalian target of rapamycin (mTOR) and 70 kDa ribosomal protein S6 kinase 2 (P70S6K) (p < 0.05).The supplementation of rapamycin downregulated the gene and protein expression of the mTOR signaling pathway, including mTOR, P70S6K, EIF4E-binding protein 1 (4EBP1), hypoxia-inducible factor 1-alpha (HIF-1α) and gene expression of glucose transporter upregulated by 8 mg/mL glucose (p < 0.05). Thus, these results indicated that the addition of 8 mg/mL glucose regulated the glucose transport and metabolism in BPTCs through the mTOR signaling pathway, thereby promoting the supply of nutrients to fetus.

Plausible mechanisms behind synergism between magnesium, vitamin D and vitamin K in management of type 2 diabetes

The escalating global prevalence of Type 2 Diabetes (T2D) necessitates effective management strategies. Nutraceuticals, addressing common dietary deficiencies in T2D patients, offer promising therapeutic options. Our work postulates the potential antidiabetic mechanisms underlying a combination therapy involving magnesium (Mg), cholecalciferol (CHOL), and menaquinone-7 (MK-7). We propose that this combination synergistically enhances insulin sensitivity and maintains adequate insulin secretion through diverse pathways. These include osteocalcin-mediated effects, modulation of insulin signal transduction, regulation of glucose transporters, and preservation of pancreatic β-cell mass. Elucidating these intricate mechanisms sheds light on the therapeutic efficacy of this combination therapy, paving the way for innovative interventions in T2D management.

Targeting YAP1-regulated Glycolysis in Fibroblast-Like Synoviocytes Impairs Macrophage Infiltration to Ameliorate Diabetic Osteoarthritis Progression.

The interplay between immune cells/macrophages and fibroblast-like synoviocytes (FLSs) plays a pivotal role in initiating synovitis; however, their involvement in metabolic disorders, including diabetic osteoarthritis (DOA), is largely unknown. In this study, single-cell RNA sequencing (scRNA-seq) is employed to investigate the synovial cell composition of DOA. A significant enrichment of activated macrophages within eight distinct synovial cell clusters is found in DOA synovium. Moreover, it is demonstrated that increased glycolysis in FLSs is a key driver for DOA patients' synovial macrophage infiltration and polarization. In addition, the yes-associated protein 1 (YAP1)/thioredoxin-interacting protein (TXNIP) signaling axis is demonstrated to play a crucial role in regulating glucose transporter 1 (GLUT1)-dependent glycolysis in FLSs, thereby controlling the expression of a series of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) which may subsequently fine-tune the infiltration of M1-polarized synovial macrophages in DOA patients and db/db diabetic OA mice. For treatment, M1 macrophage membrane-camouflaged Verteporfin (Vt)-loaded PLGA nanoparticles (MVPs) are developed to ameliorate DOA progression by regulating the YAP1/TXNIP signaling axis, thus suppressing the synovial glycolysis and the infiltration of M1-polarized macrophages. The results provide several novel insights into the pathogenesis of DOA and offer a promising treatment approach for DOA.

Regulated dynamic subcellular GLUT4 localization revealed by proximal proteome mapping in human muscle cells.

Regulation of glucose transport, which is central for control of whole-body metabolism, is determined by the amount of GLUT4 glucose transporter (also known as SLC2A4) in the plasma membrane (PM) of fat and muscle cells. Physiologic signals [such as activated insulin receptor or AMP-activated protein kinase (AMPK)] increase PM GLUT4. Here, we show that the distribution of GLUT4 between the PM and interior of human muscle cells is dynamically maintained, and that AMPK promotes PM redistribution of GLUT4 by regulating exocytosis and endocytosis. Stimulation of exocytosis by AMPK is mediated by Rab10 and the Rab GTPase-activating protein TBC1D4. APEX2 proximity mapping reveals that GLUT4 traverses both PM-proximal and PM-distal compartments in unstimulated muscle cells, further supporting retention of GLUT4 by a constitutive retrieval mechanism. AMPK-stimulated translocation involves GLUT4 redistribution among the same compartments traversed in unstimulated cells, with a significant recruitment of GLUT4 from the Golgi and trans-Golgi network compartments. Our comprehensive proximal protein mapping provides an integrated, high-density, whole-cell accounting of the localization of GLUT4 at a resolution of ∼20 nm that serves as a structural framework for understanding the molecular mechanisms regulating GLUT4 trafficking downstream of different signaling inputs in a physiologically relevant cell type.

Dysfunctional cerebral glucose transport in Alzheimer’s Disease

AbstractBackgroundGlucose is the primary energy source required for the homeostatic function of the brain. Glucose transporter 1 (GLUT1) present at the blood‐brain barrier is a key regulator of glucose transport into the brain. Reduced GLUT1 expression is shown to exacerbate Alzheimer’s pathology in rodent models. Here we aimed to establish whether there are regional differences in ineffective glucose transport amongst people living with Alzheimer’s disease.Method125 participants diagnosed with Alzheimer’s dementia, with an [18F]FDG scan with atrial input were enrolled. All participants underwent 3‐tesla magnetic resonance imaging and [18F]FDG scan with continuous and discrete arterial sampling. Spectral analysis was performed to create 1‐minute input‐response function parametric maps. To produce glucose transfer maps we applied the following equation; K1 ⁎ Ca / τ (K1 = 1‐minute IRF map, Ca = Plasma glucose concentration, τ = 1.48 a lumped constant). Glucose transfer maps were then coregistered to the participants’ structural MRI and normalised to MNI space. Regional mean glucose transfer was then calculated for the anterior cingulate cortex, frontal lobe, hippocampus, parahippocampus, occipital lobe, parietal lobe, posterior cingulate cortex, striatum, temporal lobe, and thalamus. A within‐subject ANOVA was then performed to evaluate the regional differences in cerebral glucose transport.ResultThe parahippocampus exhibited the lowest rate of glucose transfer in comparison to all other regions (p &lt; 0.001), followed by the hippocampus. The striatum and occipital lobe demonstrated the regions of the highest mean glucose transportation from blood to the brain. In terms of brain lobes, the temporal lobe showed the lowest rates of glucose transfer, followed by the parietal lobe, then frontal and occipital (p &lt; 0.001).ConclusionWe demonstrate dysfunctional BBB glucose transport in Alzheimer’s disease, with prominent glucose transport abnormalities localised in the parahippocampus. Impaired glucose transport was most apparent within temporal lobe structures. Targeting glucose transfer may be an effective way of treating Alzheimer’s disease.

Ageing-Related Alterations in Renal Epithelial Glucose Transport.

The kidney plays a crucial role in glucose homeostasis by regulating glucose transport. We aimed to investigate the impact of alterations in glucose transport on glucose metabolism during ageing. Adult male Sprague Dawley rats were divided into five groups: 3-month, 6-month, and 12-month control groups, and 6- and 12-month groups receiving the hydrogen sulfide donor molecule GYY4137. The study found that, as age increased, daily urinary uric acid and protein levels increased in the 12-month group. Blood sugar level and HOMA-IR index increased in the 12-month group, and were partially improved by GYY4137. The kidney tissue showed mild glomerulosclerosis in the 12-month group, which was diminished by GYY4137. Gene expression analysis showed decreased sirtuin and increased p21 expression in the aging groups. Increased SGLT1 and SGLT2 expression was observed in the 12-month group, which was reversed by GYY4137. Both GLUT1 and GLUT2 expression was increased in the 6- and 12-month groups, and reversed by GYY4137 in the 12-month group. The study concluded that aging was associated with increased blood sugar levels and the HOMA-IR index, and the abundance of renal glucose transporters increased as aging progressed. GYY4137 effectively reversed aging-related alterations in glucose homeostasis and renal epithelial transporters.

The effect of ellagic acid on the metabolic syndrome: A review article

Objective(s): Metabolic syndrome is a collection of metabolic abnormalities that includes hyperglycemia, dyslipidemia, hypertension, and obesity. Ellagic acid is found in various fruits and vegetables. It has been reported to have several pharmacological properties, such as antibacterial, antifungal, antiviral, anti-inflammatory, hepatoprotective, cardioprotective, chemopreventive, neuroprotective, gastroprotective, and antidiabetic. Our current study aims to shed light on the probable efficiency of ellagic acid in managing metabolic syndrome and its complications. Materials and methodsTo prepare the present review, the databases or search engines utilized included Scopus, PubMed, Science Direct, and Google Scholar, and relevant articles have been gathered with no time limit until March 2023. ResultsSeveral investigations indicated that ellagic acid could be a potent compound for the treatment of many disorders such as diabetes, hypertension, and hyperlipidemia by various mechanisms, including increasing insulin secretion, insulin receptor substrate protein 1 expression, regulating glucose transporter 4, triglyceride, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), attenuating tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), reactive oxygen species (ROS), malondialdehyde (MDA), and oxidative stress in related tissues. Furthermore, ellagic acid ameliorates mitochondrial function, upregulates uncoupling protein 1 (found in brown and white adipose tissues), and regulates blood levels of nitrate/nitrite and vascular relaxations in response to acetylcholine and sodium nitroprusside. ConclusionEllagic acid can treat or manage metabolic syndrome and associated complications, according to earlier studies. To validate the beneficial effects of ellagic acid on metabolic syndrome, additional preclinical and clinical research is necessary.

METTL3 regulates glucose transporter expression in placenta exposed to hyperglycemia through the mTOR signaling pathway.

Alterations in the placental expression of glucose transporters (GLUTs), the crucial maternal-fetal nutrient transporters, have been found in women with hyperglycemia in pregnancy (HIP). However, there is still uncertainty about the underlying effect of the high-glucose environment on placental GLUTs expression in HIP. We quantitatively evaluated the activity of mammalian target of rapamycin (mTOR) and expression of GLUTs (GLUT1, GLUT3, and GLUT4) in the placenta of women with normal pregnancies (CTRL, n = 12) and pregnant women complicated with poorly controlled type 2 diabetes mellitus (T2DM, n = 12) by immunohistochemistry. In addition, BeWo cells were treated with different glucose concentrations to verify the regulation of hyperglycemia. Then, changes in the expression of GLUTs following the activation or suppression of the mTOR pathway were also assessed using MHY1485/rapamycin (RAPA) treatment or small interfering RNA (siRNA)-mediated silencing approaches. Moreover, we further explored the alteration and potential upstream regulatory role of methyltransferase-like 3 (METTL3) when exposed to hyperglycemia. mTOR, phosphorylated mTOR (p-mTOR), and GLUT1 protein levels were upregulated in the placenta of women with T2DM compared with those CTRL. In BeWo cells, mTOR activity increased with increasing glucose concentration, and the expression of GLUT1, GLUT3, and GLUT4 as well as GLUT1 cell membrane translocation were upregulated by hyperglycemia to varying degrees. Both the drug-mediated and genetic depletion of mTOR signaling in BeWo cells suppressed GLUTs expression, whereas MHY1485-induced mTOR activation upregulated GLUTs expression. Additionally, high glucose levels upregulated METTL3 expression and nuclear translocation, and decreasing METTL3 levels suppressed GLUTs expression and mTOR activity and vice versa. Furthermore, in METTL3 knockdown BeWo cells, the inhibitory effect on GLUTs expression was eliminated by activating the mTOR signaling pathway using MHY1485. High-glucose environment-induced upregulation of METTL3 in trophoblasts regulates the expression of GLUTs through mTOR signaling, contributing to disordered nutrient transport in women with HIP.

MiRNA Associated With Glucose Transporters in Oral Squamous Cell Carcinoma: A Systematic Review.

Oral squamous cell carcinoma (OSCC) is a malignancy of the oral cavity with poor prognosis. Dysregulation in glycolytic pathways involving glucose transporters (GLUT) has been implicated in poor prognosis. Furthermore, GLUT expression in cancer cells is regulated by several miRNAs. However, there is a lack of data about miRNA involved in the regulation of GLUT in OSCC. The objective is to evaluate the role of miRNA in the regulation of GLUT in OSCC. Data sources include PubMed (MEDLINE), Scopus, and Web of Science. Studies evaluating the miRNA involved or associated with the regulation of GLUT in OSCC were included in the systematic review. Data pertaining to GLUT and associated miRNA expression were extracted from studies. Qualitative assessment was carried out for GLUT and miRNA. The Newcastle-Ottawa Scale was used for quality assessment. Ten study articles were included after analyzing 4675 papers. These studies evaluated the GLUT and miRNA expression between healthy and OSCC samples. There are variable expression patterns of GLUT in OSCC. Furthermore, it was dependent on miRNA. The GLUT1 and GLUT-3 were detected more frequently in OSCC, while no study reveals the expression of GLUT2, GLUT4, GLUT7, GLUT8, GLUT13, SGLT1, and SGLT2 with miRNA regulation. However, there was insufficient evidence on specific miRNA linked to GLUT1 or GLUT3 expression. There is evidence of the role of miRNA in the regulation of GLUT especially GLUT1 and GLUT3 in OSCC; however, a specific relation to miRNA was understudied.In the future, studies exploring a clearer understanding of the association between miRNA and the GLUT metabolic pathway in relation to OSCC are warranted. Furthermore, association of miRNA and GLUT with progression of disease, disease resistance, and prognosis is assessed for better treatment outcomes.

Optimisation preparation, physicochemical properties, and glucose transport regulation by polysaccharides from Liubao brick tea

AbstractIn this study, a water-soluble novel polysaccharide called TPS was successfully prepared and isolated from Liubao tea. The optimal extraction conditions resulted in a yield of 10.70% for the crude TPS. The purified TPS exhibited unique physicochemical properties and structural characteristics. It was identified as an acidic polysaccharide with trace binding proteins, with a →4)-α-D-Galp-(1→) residue. The purified TPS had a dense and uneven appearance, potential crystallisation characteristics, and structural stability. Importantly, it demonstrated the ability to inhibit glucose transport in Caco-2 cells by down-regulating the expression of sodium/glucose cotransporter 1 (SGLT1) and glucose transporter 2 (GLUT2), leading to a hypoglycemic effect. These findings highlight the potential of TPS from Liubao tea as a functional food or additive with hypoglycaemic properties.

Energy (and Reactive Oxygen Species Generation) Saving Distribution of Mitochondria for the Activation of ATP Production in Skeletal Muscle.

Exercise produces oxidants from a variety of intracellular sources, including NADPH oxidases (NOX) and mitochondria. Exercise-derived reactive oxygen species (ROS) are beneficial, and the amount and location of these ROS is important to avoid muscle damage associated with oxidative stress. We discuss here some of the evidence that involves ROS production associated with skeletal muscle contraction and the potential oxidative stress associated with muscle contraction. We also discuss the potential role of H2O2 produced after NOX activation in the regulation of glucose transport in skeletal muscle. Finally, we propose a model based on evidence for the role of different populations of mitochondria in skeletal muscle in the regulation of ATP production upon exercise. The subsarcolemmal population of mitochondria has the enzymatic and metabolic components to establish a high mitochondrial membrane potential when fissioned at rest but lacks the capacity to produce ATP. Calcium entry into the mitochondria will further increase the metabolic input. Upon exercise, subsarcolemmal mitochondria will fuse to intermyofibrillar mitochondria and will transfer the mitochondria membrane potential to them. These mitochondria are rich in ATP synthase and will subsequentially produce the ATP needed for muscle contraction in long-term exercise. These events will optimize energy use and minimize mitochondria ROS production.