A narrative review: exploring viral-induced malignancies through the lens of dysregulated cellular metabolism and glucose transporters.

INTRODUCTION: In this narrative review, we unravel the complex interplay between oncogenic viruses, cellular metabolism, and glucose transporter (GLUT) dysregulation in viral-induced malignancies. METHODS: By explaining the diverse mechanisms through which seven major oncoviruses manipulate metabolic pathways and GLUT expression, particularly GLUT1, we provide novel insights into the critical role of metabolic reprogramming in viral replication and oncogenesis. RESULTS: Our exploration of the molecular pathways targeted by viral oncoproteins reveals a similarity between the metabolic alterations induced by viral infections and those observed in neoplastic transformation. A key finding of our review is the overexpression of GLUTs, particularly GLUT1, as a hallmark of both viral infections and many cancers. CONCLUSIONS: By elucidating the complex interplay between viral oncoproteins, oncogene activation, tumor suppressor gene loss, and GLUT overexpression, we highlight the potential of GLUTs as novel targets for diagnosis, prognosis, and therapy of viral-induced malignancies.

Regulation and Role of Adiponectin Secretion in Rat Ovarian Granulosa Cells.

Adiponectin is an important adipokine involved in glucose and lipid metabolism, but its secretion and potential role in regulating glucose utilization during ovarian development remains unclear. This study aims to investigate the mechanism and effects of follicle-stimulating hormones (FSHs) on adiponectin secretion and its following impact on glucose transport in the granulosa cells of rat ovaries. A range of experimental techniques were utilized to test our research, including immunoblotting, immunohistochemistry, immunofluorescence, ELISA, histological staining, real-time quantitative PCR, and transcriptome analysis. The immunohistochemistry results indicated that adiponectin was primarily located in the granulosa cells of rat ovaries. In primary granulosa cells cultured in vitro, both Western blot and immunofluorescence assays demonstrated that FSH significantly induced adiponectin secretion within 2 h of incubation, primarily via the PKA signaling pathway rather than the PI3K/AKT pathway. Concurrently, the addition of the AdipoR1/AdipoR2 dual agonist AdipoRon to the culture medium significantly stimulated the protein expression of GLUT1 in rat granulosa cells, resulting in enhanced glucose absorption. Consistent with these in vitro findings, rats injected with eCG (which shares structural and functional similarities with FSH) exhibited significantly increased adiponectin levels in both the ovaries and blood. Moreover, there was a notable elevation in mRNA and protein levels of AdipoRs and GLUTs following eCG administration. Transcriptomic analysis further revealed a positive correlation between the expression of the intraovarian adiponectin system and glucose transporter. The present study represents a novel investigation, demonstrating that FSH stimulates adiponectin secretion in ovarian granulosa cells through the PKA signaling pathway. This mechanism potentially influences glucose transport (GLUT1) and utilization within the ovaries.

The effect of different boron compounds on nutrient digestibility, intestinal nutrient transporters, and liver lipid metabolism.

BACKGROUND: Gastrointestinal health is essential for maintaining a healthy lifestyle. Improving nutrient absorption and energy metabolism are the critical targets for intestinal health. This study aimed to determine the effects of different boron (B) derivatives on nutrient digestibility, intestinal nutrient transporters, and lipid metabolism in rats. METHODS: Twenty-one rats were allocated to three groups (n = 7) as follows: (i) Control, (ii) Sodium pentaborate pentahydrate (SPP), and (iii) boric acid (BA). The rats were fed a chow diet (AIN-93M) and supplemented with 8 mg/kg elemental B from SPP (45.2 mg/kg BW) and BA (42.7 mg/kg BW) via oral gavage every other day for 12 weeks. The nutrient digestibility of rats in each group was measured using the indigestible indicator (chromium oxide, Cr2 O3, 0.20%). At the end of the experiment, animals were decapitated by cervical dislocation and jejunum, and liver samples were taken from each animal. The nutrient transporters and lipid-regulated transcription factors were determined by RT-PCR. RESULTS: The nutrient digestibility (except for ash) was increased by SPP and BA supplementation (p < 0.05). SPP and BA-supplemented rats had higher jejunal glucose transporter 1 (GLUT1), GLUT2, GLUT5, sodium-dependent glucose transporter 1 (SGLT1), fatty acid transport protein-1 (FATP1), and FATP4 mRNA expression levels compared to nonsupplemented rats (p < 0.0001). BA-supplemented rats had remarkably higher peroxisome proliferator-activated receptor gamma (PPARγ) levels than nonsupplemented rats (p < 0.0001). In contrast, sterol regulatory element-binding protein 1c (SREBP-1c), liver X receptor alpha (LxR-α), and fatty acid synthase (FAS) levels decreased by SPP supplementation compared to other groups (p < 0.05). DISCUSSION: SPP and BA administration enhanced nutrient digestibility, intestinal nutrient transporters, and liver lipid metabolism in rats.

Synthetic Monosaccharide Channels: Size-Selective Transmembrane Transport of Glucose and Fructose Mediated by Porphyrin Boxes.

Here we report synthetic monosaccharide channels built with shape-persistent organic cages, porphyrin boxes (PBs), that allow facile transmembrane transport of glucose and fructose through their windows. PBs show a much higher transport rate for glucose and fructose over disaccharides such as sucrose, as evidenced by intravesicular enzyme assays and molecular dynamics simulations. The transport rate can be modulated by changing the length of the alkyl chains decorating the cage windows. Insertion of a linear pillar ligand into the cavity of PBs blocks the monosaccharide transport. In vitro cell experiment shows that PBs transport glucose across the living-cell membrane and enhance cell viability when the natural glucose transporter GLUT1 is blocked. Time-dependent live-cell imaging and MTT assays confirm the cyto-compatibility of PBs. The monosaccharide-selective transport ability of PBs is reminiscent of natural glucose transporters (GLUTs), which are crucial for numerous biological functions.

Importance of GLUT Transporters in Disease Diagnosis and Treatment.

Facilitative sugar transporters (GLUTs) are the primary method of sugar uptake in all mammalian cells. There are 14 different types of those transmembrane proteins, but they transport only a handful of substrates, mainly glucose and fructose. This overlap and redundancy contradict the natural tendency of cells to conserve energy and resources, and has led researchers to hypothesize that different GLUTs partake in more metabolic roles than just sugar transport into cells. Understanding those roles will lead to better therapeutics for a wide variety of diseases and disorders. In this review we highlight recent discoveries of the role GLUTs play in different diseases and disease treatments.

Brain Metabolic Alterations in Alzheimer's Disease.

The brain is one of the most energy-consuming organs in the body. Satisfying such energy demand requires compartmentalized, cell-specific metabolic processes, known to be complementary and intimately coupled. Thus, the brain relies on thoroughly orchestrated energy-obtaining agents, processes and molecular features, such as the neurovascular unit, the astrocyte-neuron metabolic coupling, and the cellular distribution of energy substrate transporters. Importantly, early features of the aging process are determined by the progressive perturbation of certain processes responsible for adequate brain energy supply, resulting in brain hypometabolism. These age-related brain energy alterations are further worsened during the prodromal stages of neurodegenerative diseases, namely Alzheimer's disease (AD), preceding the onset of clinical symptoms, and are anatomically and functionally associated with the loss of cognitive abilities. Here, we focus on concrete neuroenergetic features such as the brain's fueling by glucose and lactate, the transporters and vascular system guaranteeing its supply, and the metabolic interactions between astrocytes and neurons, and on its neurodegenerative-related disruption. We sought to review the principles underlying the metabolic dimension of healthy and AD brains, and suggest that the integration of these concepts in the preventive, diagnostic and treatment strategies for AD is key to improving the precision of these interventions.

Late-Stage Functionalization through Click Chemistry Provides GLUT5-Targeting Glycoconjugate as a Potential PET Imaging Probe.

The targeting of facilitative sugar transporters (GLUTs) has been utilized in the development of tools for diagnostics and therapy. The interest in this area is promoted by the phenomenon of alterations in cellular metabolic processes that are linked to multitudes of metabolic disorders and diseases. However, nonspecific targeting (e.g., glucose-transporting GLUTs) leads to a lack of disease detection efficiency. Among GLUTs, GLUT5 stands out as a prominent target for developing specific molecular tools due to its association with metabolic diseases, including cancer. This work reports a non-radiolabeled fluoride (19F) coumarin-based glycoconjugate of 2,5-anhydro-D-mannitol as a potential PET imaging probe that targets the GLUT5 transporter. Inherent fluorescent properties of the coumarin fluorophore allowed us to establish the probe's uptake efficiency and GLUT5-specificity in a GLUT5-positive breast cell line using fluorescence detection techniques. The click chemistry approach employed in the design of the probe enables late-stage functionalization, an essential requirement for obtaining the radiolabeled analog of the probe for future in vivo cancer imaging applications. The high affinity of the probe to GLUT5 allowed for the effective uptake in nutrition-rich media.

Inhibition of the facilitative sugar transporters (GLUTs) by tea extracts and catechins.

Tea polyphenolics have been suggested to possess blood glucose lowering properties by inhibiting sugar transporters in the small intestine and improving insulin sensitivity. In this report, we studied the effects of teas and tea catechins on the small intestinal sugar transporters, SGLT1 and GLUTs (GLUT1, 2 and 5). Green tea extract (GT), oolong tea extract (OT), and black tea extract (BT) inhibited glucose uptake into the intestinal Caco-2 cells with GT being the most potent inhibitor (IC50 : 0.077 mg/mL), followed by OT (IC50 : 0.136 mg/mL) and BT (IC50 : 0.56 mg/mL). GT and OT inhibition of glucose uptake was partial non-competitive, with an inhibitor constant (Ki ) = 0.0317 and 0.0571 mg/mL, respectively, whereas BT was pure non-competitive, Ki  = 0.36 mg/mL. Oocytes injected to express small intestinal GLUTs were inhibited by teas, but SGLT1 was not. Furthermore, catechins present in teas were the predominant inhibitor of glucose uptake into Caco-2 cells, and gallated catechins the most potent: CG > ECG > EGCG ≥ GCG when compared to the non-gallated catechins (C, EC, GC, and EGC). In Caco-2 cells, individual tea catechins reduced the SGLT1 gene, but not protein expression levels. In contrast, GLUT2 gene and protein expression levels were reduced after 2 hours exposure to catechins but increased after 24 hours. These in vitro studies suggest teas containing catechins may be useful dietary supplements capable of blunting postprandial glycaemia in humans, including those with or at risk to Type 2 diabetes mellitus.

The IGF-1/GH-GLUTs-plasma glucose regulating axis in hybrid grouper (Epinephelus fuscoguttatus♀ × epinephelus lanceolatus♂) fed a high-carbohydrate diet.

The carnivorous teleost fish is often intolerant to high levels of postprandial plasma glucose. This study aimed to evaluate the effects of insulin-like growth factor-1 (IGF-1) and growth hormone (GH) administrations on plasma glucose levels and expression of glucose transporters (GLUTs) in various tissues of hybrid grouper, and hence to further clarify the hormone-GLUTs-plasma glucose regulating axis. Twenty-four experimental fish (average body weight: 77.5 ± 5.4 g) were selected and injected with recombinant human IGF-1 (0.2 µg/g body weight) and PBS (0.01 mol/L) in enterocoelia, respectively, and in the GH injected experiment, the same quantity of fish (average body weight: 103.8 ± 5.8 g) were administrated with GH at a dose of 0.5 µg/g body weight or with PBS at a dose of 0.01 mol/L. Results showed that plasma glucose level was significantly (P < 0.05) declined by the IGF-1 administration but elevated by the GH administration. Plasma IGF-1 concentration was significantly (P < 0.01) elevated by the IGF-1 administration, while GH concentration did not significantly (P ≥ 0.05) respond to the GH administration. The relative mRNA levels of insulin-like growth factor-1 receptor a (IGF-Ra) in liver and muscle were decreased significantly with the IGF-1 administration, and a similar variation tendency was also found in insulin-like growth factor-1 receptor b (IGF-Rb) in liver, muscle and adipose tissues. Besides, the relative mRNA level of insulin receptor (IRS) in liver was significantly increased in the IGF-1 administrated group. After the GH administration, the mRNA levels of hepatic growth factor receptor 2 (GHR2) and IGF-1 were significantly elevated. As for GLUTs, the relative mRNA levels of GLUT1 and GLUT2 in liver were obviously elevated by the IGF-1 administration, while the mRNA level of GLUT4 in muscle was reduced. In liver, the protein levels of GLUT1, 2 and 4 were significantly elevated by the IGF-1 administration, and in adipose, only GLUT1 was observed to have a significantly increased protein level. The mRNA expression of GLUTs was less affected by the GH administration. The protein level of GLUT1 in liver was significantly reduced by the GH administration, while in adipose, it was significantly increased. The protein level of GLUT2 in liver or adipose showed an opposite variation as that of GLUT1. Overall, IGF-1 had a hypoglycemic effect on hybrid grouper, and this probably was through up-regulating the protein levels of hepatic GLUT1, 2 and 4 and adipose GLUT1. GH showed an opposite role in regulating plasma glucose level as IGF-1.

Glucose transporters in pancreatic islets.

The fine-tuning of glucose uptake mechanisms is rendered by various glucose transporters with distinct transport characteristics. In the pancreatic islet, facilitative diffusion glucose transporters (GLUTs), and sodium-glucose cotransporters (SGLTs) contribute to glucose uptake and represent important components in the glucose-stimulated hormone release from endocrine cells, therefore playing a crucial role in blood glucose homeostasis. This review summarizes the current knowledge about cell type-specific expression profiles as well as proven and putative functions of distinct GLUT and SGLT family members in the human and rodent pancreatic islet and further discusses their possible involvement in onset and progression of diabetes mellitus. In context of GLUTs, we focus on GLUT2, characterizing the main glucose transporter in insulin-secreting ß-cells in rodents. In addition, we discuss recent data proposing that other GLUT family members, namely GLUT1 and GLUT3, render this task in humans. Finally, we summarize latest information about SGLT1 and SGLT2 as representatives of the SGLT family that have been reported to be expressed predominantly in the α-cell population with a suggested functional role in the regulation of glucagon release.

Expression pattern of GLUT 1, 5, 8 and citrate synthase transcripts in buffalo (Bubalus bubalis) preimplantation embryos produced in vitro and derived in vivo.

In vitro-produced (IVP) embryos are reported to be developmentally lesser competent than in vivo-derived (IVD) embryos and supposed to differ in the expression of genes related with glucose metabolism. So, the present study was conducted to analyse the expression pattern of GLUT 1, 5, 8 and citrate synthase (CS) in oocytes and embryos produced in vivo or in vitro in buffalo. IVD embryos were obtained from 18 superovulated buffaloes. IVP embryos were obtained from slaughterhouse-derived oocytes subsequently subjected to in vitro fertilization and culture. Total RNA was isolated from different stages of oocytes (immature and in vitro matured) and embryos (8-16 cell to blastocysts of IVP embryos and morula to blastocysts of IVD embryos). Results demonstrated that the expression of GLUT1, GLUT 8 increased from 8 to 16 cells to blastocyst and was significantly (p < .05) higher in IVP embryos. Expression of both genes was (p < .05) higher in IVD than in IVP blastocysts; though GLUT5 transcripts were not detected at 8- to 16-cell stage IVP embryos, significantly (p < .05) higher transcripts were found at morula and blastocyst stages irrespective of embryo source with significantly (p < .05) higher expression in IVD embryos compared to IVP embryos. No significant difference was observed in citrate synthase expression in embryos at morula stage irrespective of the embryo source while significantly (p < .05) higher transcript level was observed at blastocyst stage with no difference between in vivo and in vitro embryos. It can be concluded that expression of GLUTs and CS is upregulated with progression of embryonic stage and expression is higher in in vivo embryos than in vitro counter parts; thus, it can be said that in vivo-produced embryos are metabolically superior to in vitro embryos.

Endogenous SHBG levels correlate with that of glucose transporters in insulin resistance model cells.

Gestational diabetes mellitus (GDM) is defined as glucose intolerance of any degree that occurs after onset of pregnancy. Sex hormone binding globulin (SHBG) plays an important regulatory role in insulin resistance and is a risk factor in GDM. In the current study, we aimed to examine whether SHBG can regulate glucose metabolism through glucose transporters (GLUTs). SHBG was transfected into established human insulin model cells and the expression of SHBG, GLUT1, GLUT3, and GLUT4 was detected and analyzed in normal cells, model cells, and all groups of transfected cells by real-time PCR and western blotting. Further, immunofluorescence staining was performed on cells from each group to observe protein expression. In insulin resistance model cells, the expression of SHBG was low, whereas that of GLUT1 was high and of GLUT3 and GLUT4 was low, when compared with expression in control cells. Moreover, the overexpression of SHBG inhibited the expression of GLUT1 mRNA and protein, and promoted the expression of GLUT3 and GLUT4. Our results indicate that SHBG could be involved in glucose metabolism through its regulation of multiple GLUTs. Transfection of SHBG into insulin-resistant cells may partially improve the level of GLUTs, providing a potential therapeutic approach for the treatment of insulin resistance in GDM. Although SHBG can regulate glucose metabolism through GLUTs and thus cause insulin resistance and induce gestational diabetes, the regulation mechanism of GLUTs mediated by SHBG has not been elucidated, which will be the focus of further studies.

Physiology of renal glucose handling via SGLT1, SGLT2 and GLUT2.

The concentration of glucose in plasma is held within narrow limits (4-10 mmol/l), primarily to ensure fuel supply to the brain. Kidneys play a role in glucose homeostasis in the body by ensuring that glucose is not lost in the urine. Three membrane proteins are responsible for glucose reabsorption from the glomerular filtrate in the proximal tubule: sodium-glucose cotransporters SGLT1 and SGLT2, in the apical membrane, and GLUT2, a uniporter in the basolateral membrane. 'Knockout' of these transporters in mice and men results in the excretion of filtered glucose in the urine. In humans, intravenous injection of the plant glucoside phlorizin also results in excretion of the full filtered glucose load. This outcome and the finding that, in an animal model, phlorizin reversed the symptoms of diabetes, has stimulated the development and successful introduction of SGLT2 inhibitors, gliflozins, in the treatment of type 2 diabetes mellitus. Here we summarise the current state of our knowledge about the physiology of renal glucose handling and provide background to the development of SGLT2 inhibitors for type 2 diabetes treatment.

Amyloid-ß oligomers transiently inhibit AMP-activated kinase and cause metabolic defects in hippocampal neurons.

AMP-activated kinase (AMPK) is a key player in energy sensing and metabolic reprogramming under cellular energy restriction. Several studies have linked impaired AMPK function to peripheral metabolic diseases such as diabetes. However, the impact of neurological disorders, such as Alzheimer disease (AD), on AMPK function and downstream effects of altered AMPK activity on neuronal metabolism have been investigated only recently. Here, we report the impact of Aß oligomers (AßOs), synaptotoxins that accumulate in AD brains, on neuronal AMPK activity. Short-term exposure of cultured rat hippocampal neurons or ex vivo human cortical slices to AßOs transiently decreased intracellular ATP levels and AMPK activity, as evaluated by its phosphorylation at threonine residue 172 (AMPK-Thr(P)172). The AßO-dependent reduction in AMPK-Thr(P)172 levels was mediated by glutamate receptors of the N-methyl-d-aspartate (NMDA) subtype and resulted in removal of glucose transporters (GLUTs) from the surfaces of dendritic processes in hippocampal neurons. Importantly, insulin prevented the AßO-induced inhibition of AMPK. Our results establish a novel toxic impact of AßOs on neuronal metabolism and suggest that AßO-induced, NMDA receptor-mediated AMPK inhibition may play a key role in early brain metabolic defects in AD.

Inhibition of GLUTs by WZB117 mediates apoptosis in blood-stage Plasmodium parasites by breaking redox balance.

Like tumour cells, during intraerythrocytic stage, Plasmodium-infected erythrocytes rely completely on glucose absorption from the blood circulation for energy metabolism. Glucose is taken up by glucose transporter 1 (GLUT1) on human red blood cells (RBCs) and glucose transporter 4 (GLUT4) on rodent RBCs. Blood-stage parasites grow rapidly; therefore, infected red blood cells (iRBCs) need much more glucose for energy. In previous study, WZB117 (2-fluoro-6-(m-hydroxybenzoyloxy) phenyl m-hydroxybenzoate) inhibits GLUT1 by binding the exofacial sugar-binding site and inhibits the insulin-sensitive GLUT4 with greater potency than its inhibition of either GLUT1 or GLUT3. In our study, WZB117 effectively inhibit the growth of blood-stage parasites. Mechanistically, WZB117 inhibited the activity of GLUTs and perturbed the glycolysis. Therefore, decreasing the glucose level increased the redox oxidative species (ROS) level and induced oxidative stress and apoptosis. The spleen can more easily clear apoptopic iRBCs than nonapoptotic iRBCs, effectively relieving hepatosplenomegaly. These findings provide important insights into the crucial role of glucose transporters (GLUTs) in Plasmodium glucose uptake during intra-erythrocytic stage, as the inhibition of GLUTs block Plasmodium infection during the erythrocytic stage.

Adiposity associated changes in serum glucose and adiponectin levels modulate ovarian steroidogenesis during delayed embryonic development in the fruit bat, Cynopterus sphinx.

The aim of the present study was to evaluate the mechanism by which embryonic development in Cynopterus sphinx is impaired during the period of increased accumulation of white adipose tissue during winter scarcity of food. The change in the mass of white adipose tissue during adipogenesis showed significant positive correlation with the circulating glucose level. But increase in circulating glucose level during the adipogenesis showed negative correlation with circulating progesterone and adiponectin levels. The in vivo study showed increased glucose uptake by the adipose tissue during adipogenesis due to increased expression of insulin receptor (IR) and glucose transporter (GLUT) 4 proteins. This study showed decline in the adiponectin level during fat accumulation. In the in vitro study, ovary treated with high doses of glucose showed impaired progesterone synthesis. This is due to decreased glucose uptake mediated decrease in the expression of luteinizing hormone-receptor, steroidogenic acute regulatory protein, IR, GLUT4 and AdipoR1 proteins. But the ovary treated with adiponectin either alone or with higher concentration of glucose showed improvement in progesterone synthesis due to increased expression of IR, GLUT4 and AdipoR1 mediated increased glucose uptake. In conclusion, increased circulating glucose level prior to winter dormancy preferably transported to white adipose tissue for fat accumulation diverting glucose away from the ovary. Consequently the decreased availability of adiponectin and glucose to the ovary and utero-embryonic unit may be responsible for impaired progesterone synthesis and delayed embryonic development. The delayed embryonic development in Cynopterus sphinx may have evolved, in part, as a mechanism to prevent pregnancy loss during the period of decreased energy availability.

[Differentiated hypoglycemic effects of baicalin, berberine and puerarin on insulin-resistance HepG2 cells].

To investigate the hypoglycemic effects of baicalin, berberine, puerarin and liquiritin on the insulin resistance (IR) cells. The IR model of HepG2 cells was established by treatment with insulin and dexamethasone for 48 h. Glucose uptake, glycogen content and cell viability were detected with different concentrations of baicalin, berberine, puerarin, liquiritin in IR-HepG2 cells. Compared with IR model group, all of intervened groups significantly increased the glucose consumption, except for liquiritin groups and 1 µmol·L⁻¹ baicalin group. Moreover, 10, 20, 50 µmol·L⁻¹ baicalin, 5, 10, 20, 50 µmol·L⁻¹ berberine and 40, 80, 160 µmol·L⁻¹ puerarin significantly elevated glycogen content in IR-HepG2 cells. Liquiritin did not show obvious hypoglycemic effect. Compared with normal group, the mRNA expression levels of GLUT1 and GLUT4 were decreased in IR-HepG2 cells according to qPCR results. 5, 20 µmol·L⁻¹ berberine decreased the mRNA expression level of GLUT1 in IR-HepG2 cells, whereas 20, 40, 80 µmol·L⁻¹ puerarin significantly elevated the mRNA expression level of GLUT1. Moreover, 10, 20, 50 µmol·L⁻¹ baicalin and 20 µmol·L⁻¹ berberine increased the mRNA expression level of GLUT4. Whereas, 40, 80 µmol·L⁻¹ puerarin decreased the mRNA expression level of GLUT4. Western blot results suggested that 10, 20, 50 µmol·L⁻¹ baicalin significantly increased the protein expressions of GLUT2 and GLUT4, whereas 20, 40, 80 µmol·L⁻¹ puerarin significantly up-regulated GLUT1 and GLUT2 proteins. In addition, 20 µmol·L⁻¹ berberine increased the protein expressions of GLUT2 and GLUT4, whereas 10 µmol·L⁻¹ berberine up-regulated GLUT4 expression. The results preliminarily suggested that baicalin, berberine and puerarin have differentiated hypoglycemic effects, which accelerate glucose transport, increase glycogen synthesis, regulate glucose metabolism and improve hepatic IR.

[Jatrorrhizine regulates GLUTs with multiple manners for hypoglycemic effect in insulin-resistance 3T3-L1 adipocytes].

This paper aimed to investigate the hypoglycemic effect and relative mechanism of jatrorrhizine in insulin-resistance (IR)-3T3-L1 adipocytes. The 3T3-L1 preadipocytes were used to induce mature adipocytes, then the stable IR model was established with 1 µmol·L⁻¹ dexamethasone. The adipocytes were divided into normal group, IR model group, rosiglitazone positive group and jatrorrhizine group (0.5, 1, 5, 10, 20 µmol·L⁻¹). After different time points (12, 24, 30, 36, 48 h) treatment, glucose content of 3T3-L1 adipocytes was detected by the glucose oxidase peroxidase method and TG content was measured by glycerol phosphate oxidase method, whereas cell viability was detected by CCK-8 assay. Furthermore, the protein expression levels of insulin receptor substrate 2 (IRS2), phosphinositide-3-kinase regulatory subunit 1(PI3KR1), phosphorylated protein B [p-AKT (Ser473)], phosph-AMP-activated protein [p-AMPK (Thr172)], and glucose transporter type 4/1/2 (GLUT4/1/2) were detected by Western blot assay. The results showed that as compared with the normal group, the glucose consumptionwas significantly decreased in IR model group(P<0.01); whereas 0.5, 1, 5, 10, 20 µmol·L⁻¹ jatrorrhizine and rosiglitazone group elevated IR-3T3-L1 cells glucose consumption (P<0.01) at 36 h and 48 h administration as compared with IR group. The optimal administration time was 48 h for jatrorrhizine. 1, 5, 10, 20 µmol·L⁻¹ of jatrorrhizine decreased the TG content in 3T3-L1 adipocytes for 48 h administration (P<0.05). The protein expression levels of IRS2, PI3KR1, p-AKT (Ser473), p-AMPK (Thr172), GLUT4/1/2 were significantly up-regulated by different concentrations of jatrorrhizine and rosiglitazone (P<0.01). The results showed that jatrorrhizine increased glucose uptake with elevated glucose consumption, whereas reduced intracellular TG content in IR-3T3-L1 adipocytes. Moreover, it intervened classic insulin signal pathway IRS2/PI3KR1/p-AKT/GLUT4 and increase AMPK protein phosphorylation level for the activation of GLUT1/4 for insulin sensibility. Thus, jatrorrhizine could effectively regulate the GLUTs with multiple manners for hypoglycemic effect.

Molecular Tools for Facilitative Carbohydrate Transporters (Gluts).

Facilitative carbohydrate transporters-Gluts-have received wide attention over decades due to their essential role in nutrient uptake and links with various metabolic disorders, including diabetes, obesity, and cancer. Endeavors directed towards understanding the mechanisms of Glut-mediated nutrient uptake have resulted in a multidisciplinary research field spanning protein chemistry, chemical biology, organic synthesis, crystallography, and biomolecular modeling. Gluts became attractive targets for cancer research and medicinal chemistry, leading to the development of new approaches to cancer diagnostics and providing avenues for cancer-targeting therapeutics. In this review, the current state of knowledge of the molecular interactions behind Glut-mediated sugar uptake, Glut-targeting probes, therapeutics, and inhibitors are discussed.

Organic chromium modifies the expression of orexin and glucose transporters of ovarian in heat-stressed laying hens.

In this study, the effect of the supplemental organic chromium (Cr) forms on the expression of ovarian orexin(hypocretin), glucose transporters (GLUTs), heat shock proteins (HSPs) andnuclear factor-kappaB (NF-κB)were investigated in laying hens (HS). Laying hens (n=1800; 16-wk-old; Lohmann LSL-Lite) were allocated to 6 random groups according to a 2 × 3 factorial trial scheme with two different environmental temperatures [Thermoneutral (TN groups; at either 22±2 °C 24 h/d)  and heat stress (HS groups; at 34±2 °C for 8 h/d, 08:00 to 17:00 h, followed by 22°C for 16 h for a period of 12 wks)], andhens reared under both environmental conditions were fed either a basal diet or the basal diet supplemented with 1.600 mg of chromium-picolinate (CrPic, 12.43% Cr) and 0.788 mg of chromium-histidinate (CrHis, 25.22% Cr) per kg of diet, delivering 200 µg elemental Cr per kg diet. HS groups showed decreased levels of orexin and GLUTs(GLUT1, GLUT4), and increased NFκB, HSP60, HSP70 and HSP90 levels compared to the TN groups in ovarian tissue of hens (P < 0.0001 for all).However, dietary chromium supplementation (CrPic-CrHis) increasedorexin and GLUTs levels and significantly reduced the NF-κB and HSPs levels making them closer to those of thermoneutral group (P < 0.0001).In conclusion, CrPic and CrHis showed supported the relief and treatment of stress complications.