scholarly journals GLUT2-Mediated Glucose Uptake and Availability Are Required for Embryonic Brain Development in Zebrafish

2014 ◽  
Vol 35 (1) ◽  
pp. 74-85 ◽  
Author(s):  
Rubén Marín-Juez ◽  
Mireia Rovira ◽  
Diego Crespo ◽  
Michiel van der Vaart ◽  
Herman P Spaink ◽  
...  
Keyword(s):  
Brain Development ◽  
Glucose Uptake ◽  
Neural Progenitor Cells ◽  
Glucose Transporter ◽  
Glucose Sensing ◽  
Glucose Transporter 2 ◽  
Glut2 Gene ◽  
Glucose Dynamics ◽  
The Brain

Glucose transporter 2 (GLUT2; gene name SLC2A2) has a key role in the regulation of glucose dynamics in organs central to metabolism. Although GLUT2 has been studied in the context of its participation in peripheral and central glucose sensing, its role in the brain is not well understood. To decipher the role of GLUT2 in brain development, we knocked down slc2a2 ( glut2), the functional ortholog of human GLUT2, in zebrafish. Abrogation of glut2 led to defective brain organogenesis, reduced glucose uptake and increased programmed cell death in the brain. Coinciding with the observed localization of glut2 expression in the zebrafish hindbrain, glut2 deficiency affected the development of neural progenitor cells expressing the proneural genes atoh1b and ptf1a but not those expressing neurod. Specificity of the morphant phenotype was demonstrated by the restoration of brain organogenesis, whole-embryo glucose uptake, brain apoptosis, and expression of proneural markers in rescue experiments. These results indicate that glut2 has an essential role during brain development by facilitating the uptake and availability of glucose and support the involvement of glut2 in brain glucose sensing.

scholarly journals „Nie popadajmy w przesadę z tą równością” – płeć mózgu, heteronorma i mistyka naukowości

Adeptus ◽  
2018 ◽  
Author(s):  
Ludmiła Janion
Keyword(s):  
Brain Development ◽  
Catholic Church ◽  
Brain Structure ◽  
Public Discourse ◽  
Right Wing ◽  
Significant Aspect ◽  
Popular Book ◽  
Scientific Justification ◽  
The Brain

„Let’s not be too eager about equality” – brain sex, heteronormativity, and the scientific mystiqueThe article analyses the role of brain sex in Polish public discourse of the last years. The authors of a popular book Brain Sex claim that differences between women and men stem from differences in the brain structure, and because of that they are universal and unchangeable; feminism is based on misrepresentation of science. This thesis was overtaken by right-wing journalists, as it gave scientific justification to conservative gender politics and contemplementarity – the gender ontology of the Catholic church. However, in the rightwing journalism a significant aspect of brain sex theory is silenced, namely, the claim that homo- and transsexuality result from disorders in brain development; they are unchangeable and should be accepted. Despite its conservative roots, brain sex was popularized in liberal media as well. The aura of science that accompanied this popular theory allowed to naturalize its anti-feminism and heteronormativity. This phenomenon is discussed on the basis of media activity of two Polish scientists who are popular both in right-wing and liberal media: Anna Grabowska and Jerzy Vetulani. Both present brain sex theory as objective, universally accepted truth, which is attacked in the name of the leftist ideology by ignorant activists who deny science. „Nie popadajmy w przesadę z tą równością” – płeć mózgu, heteronorma i mistyka naukowościArtykuł analizuje rolę płci mózgu w polskim dyskursie publicznym ostatnich lat. Autorzy niezwykle popularnej w Polsce książki Płeć mózgu twierdzą, że różnice między kobietami i mężczyznami wynikają z różnic w budowie mózgów, a przez to są uniwersalne i niezmienne, feminizm zaś jest oparty na fałszowaniu nauki. Teza ta została podchwycona przez prawicowych publicystów, ponieważ nadawała naukową legitymację konserwatywnej polityce płci oraz komplementaryzmowi – ontologii płci przyjętej przez Kościół katolicki. W prawicowym piśmiennictwie przemilcza się jednak istotny aspekt płci mózgu, mianowicie twierdzenie, że homo- i transseksualność wynikają z wad w rozwoju mózgu, są niezmienne i powinny być akceptowane. Mimo swoich konserwatywnych korzeni płeć mózgu była popularyzowana także w mediach liberalnych. Nimb naukowości, którym otaczany był popularny pogląd, pozwalał naturalizować związane z nim antyfeminizm i heteronormatywność. Zjawisko to omówione jest na podstawie działalności popularyzatorskiej dwojga naukowców, cieszących się popularnością zarówno w prawicowych, jak i liberalnych mediach: Anny Grabowskiej i Jerzego Vetulaniego. Oboje przedstawiali płeć mózgu jako obiektywną, powszechnie uznawaną naukową prawdę, z którą w imię lewicowej ideologii próbują walczyć nieakceptujący ustaleń nauki aktywiści.

scholarly journals Alleviative Effect of Ruellia tuberosa L. on Insulin Resistance and Abnormal Lipid Accumulation in TNF-α-Treated FL83B Mouse Hepatocytes

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Hong-Jie Chen ◽  
Chih-Yuan Ko ◽  
Jian-Hua Xu ◽  
Yu-Chu Huang ◽  
James Swi-Bea Wu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Ethyl Acetate ◽  
Glucose Uptake ◽  
Insulin Signaling ◽  
Lipid Accumulation ◽  
Glucose Transporter ◽  
Peroxisome Proliferator ◽  
Glucose Transporter 2 ◽  
Tnf Α ◽  
Mouse Hepatocytes

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease, and most patients with T2DM develop nonalcoholic fatty liver disease (NAFLD). Both diseases are closely linked to insulin resistance (IR). Our previous studies demonstrated that Ruellia tuberosa L. (RTL) extract significantly enhanced glucose uptake in the skeletal muscles and ameliorated hyperglycemia and IR in T2DM rats. We proposed that RTL might be via enhancing hepatic antioxidant capacity. However, the potent RTL bioactivity remains unidentified. In this study, we investigated the effects of RTL on glucose uptake, IR, and lipid accumulation in vitro to mimic the T2DM accompanied by the NAFLD paradigm. FL83B mouse hepatocytes were treated with tumor necrosis factor-α (TNF-α) to induce IR, coincubated with oleic acid (OA) to induce lipid accumulation, and then, treated with RTL fractions, fractionated with n-hexane or ethyl acetate (EA), from column chromatography, and analyzed by thin-layer chromatography. Our results showed that the ethyl acetate fraction (EAf2) from RTL significantly increased glucose uptake and suppressed lipid accumulation in TNF-α plus OA-treated FL83B cells. Western blot analysis showed that EAf2 from RTL ameliorated IR by upregulating the expression of insulin-signaling-related proteins, including protein kinase B, glucose transporter-2, and peroxisome proliferator-activated receptor alpha in TNF-α plus OA-treated FL83B cells. The results of this study suggest that EAf2 from RTL may improve hepatic glucose uptake and alleviate lipid accumulation by ameliorating and suppressing the hepatic insulin signaling and lipogenesis pathways, respectively, in hepatocytes.

scholarly journals Dynamic N6-methyladenosine RNA methylation in brain and diseases

Epigenomics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 371-380 ◽  
Author(s):  
Andrew M Shafik ◽  
Emily G Allen ◽  
Peng Jin
Keyword(s):  
Brain Development ◽  
Rna Modification ◽  
Normal Brain ◽  
Biological Processes ◽  
Future Directions ◽  
Body Of Knowledge ◽  
Neuropsychiatric Diseases ◽  
The Brain ◽  
Normal Brain Development

N6-methyladenosine (m6A) is a dynamic RNA modification that regulates various aspects of RNA metabolism and has been implicated in many biological processes and transitions. m6A is highly abundant in the brain; however, only recently has the role of m6A in brain development been a focus. The machinery that controls m6A is critically important for proper neurodevelopment, and the precise mechanisms by which m6A regulates these processes are starting to emerge. However, the role of m6A in neurodegenerative and neuropsychiatric diseases still requires much elucidation. This review discusses and summarizes the current body of knowledge surrounding the function of the m6A modification in regulating normal brain development, neurodegenerative diseases and outlines possible future directions.

scholarly journals A Protective Role of Arecoline Hydrobromide in Experimentally Induced Male Diabetic Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Indraneel Saha ◽  
Joydeep Das ◽  
Biswaranjan Maiti ◽  
Urmi Chatterji
Keyword(s):  
Glucose Transporter ◽  
Serum Insulin ◽  
Diabetic Rats ◽  
Receptor Expression ◽  
Cell Regeneration ◽  
Sialic Acid Content ◽  
Glucose Transporter 2 ◽  
Experimentally Induced

Objectives.Arecoline, the most potent and abundant alkaloid of betel nut, causes elevation of serum testosterone and androgen receptor expression in rat prostate, in addition to increase in serum insulin levels in rats, leading to insulin resistance and type 2 diabetes-like conditions. This study investigated the role of arecoline on the reproductive status of experimentally induced type 1 diabetic rats.Methods.Changes in the cellular architecture were analyzed by transmission electron microscopy. Blood glucose, serum insulin, testosterone, FSH, and LH were assayed. Fructose content of the coagulating gland and sialic acid content of the seminal vesicles were also analyzed.Results.Arecoline treatment for 10 days at a dose of 10 mg/kg of body weight markedly facilitatedβ-cell regeneration and reversed testicular and sex accessory dysfunctions by increasing the levels of serum insulin and gonadotropins in type 1 diabetic rats. Critical genes related toβ-cell regeneration, such as pancreatic and duodenal homeobox 1 (pdx-1) and glucose transporter 2 (GLUT-2), were found to be activated by arecoline at the protein level.Conclusion.It can thus be suggested that arecoline is effective in ameliorating the detrimental effects caused by insulin deficiency on gonadal and male sex accessories in rats with type 1 diabetes.

scholarly journals Neuropeptide Y in normal eating and in genetic and dietary-induced obesity

2006 ◽  
Vol 361 (1471) ◽  
pp. 1159-1185 ◽  
Author(s):  
B Beck
Keyword(s):  
Neuropeptide Y ◽  
Diet Composition ◽  
High Energy ◽  
Glucose Sensing ◽  
Feeding Regulation ◽  
Treatment Of Obesity ◽  
The Brain ◽  
Diet Type

Neuropeptide Y (NPY) is one the most potent orexigenic peptides found in the brain. It stimulates food intake with a preferential effect on carbohydrate intake. It decreases latency to eat, increases motivation to eat and delays satiety by augmenting meal size. The effects on feeding are mediated through at least two receptors, the Y1 and Y5 receptors. The NPY system for feeding regulation is mostly located in the hypothalamus. It is formed of the arcuate nucleus (ARC), where the peptide is synthesized, and the paraventricular (PVN), dorsomedial (DMN) and ventromedial (VMN) nuclei and perifornical area where it is active. This activity is modulated by the hindbrain and limbic structures. It is dependent on energy availability, e.g. upregulation with food deprivation or restriction, and return to baseline with refeeding. It is also sensitive to diet composition with variable effects of carbohydrates and fats. Leptin signalling and glucose sensing which are directly linked to diet type are the most important factors involved in its regulation. Absence of leptin signalling in obesity models due to gene mutation either at the receptor level, as in the Zucker rat, the Koletsky rat or the db / db mouse, or at the peptide level, as in ob / ob mouse, is associated with increased mRNA abundance, peptide content and/or release in the ARC or PVN. Other genetic obesity models, such as the Otsuka–Long–Evans–Tokushima Fatty rat, the agouti mouse or the tubby mouse, are characterized by a diminution in NPY expression in the ARC nucleus and by a significant increase in the DMN. Further studies are necessary to determine the exact role of NPY in these latter models. Long-term exposure to high-fat or high-energy palatable diets leads to the development of adiposity and is associated with a decrease in hypothalamic NPY content or expression, consistent with the existence of a counter-regulatory mechanism to diminish energy intake and limit obesity development. On the other hand, an overactive NPY system (increased mRNA expression in the ARC associated with an upregulation of the receptors) is characteristic of rats or rodent strains sensitive to dietary-induced obesity. Finally, NPY appears to play an important role in body weight and feeding regulation, and while it does not constitute the only target for drug treatment of obesity, it may nevertheless provide a useful target in conjunction with others.

scholarly journals Necrotizing Enterocolitis, Gut Microbiota, and Brain Development: Role of the Brain-Gut Axis

Neonatology ◽  
2019 ◽  
Vol 115 (4) ◽  
pp. 423-431 ◽  
Author(s):  
Hendrik J. Niemarkt ◽  
Tim G. De Meij ◽  
Christ-jan van Ganzewinkel ◽  
Nanne K.H. de Boer ◽  
Peter Andriessen ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Brain Development ◽  
Necrotizing Enterocolitis ◽  
The Brain

scholarly journals Glucose Uptake in Trichoderma harzianum: Role of gtt1

2003 ◽  
Vol 2 (4) ◽  
pp. 708-717 ◽  
Author(s):  
Jesús Delgado-Jarana ◽  
Miguel Ángel Moreno-Mateos ◽  
Tahía Benítez
Keyword(s):  
Gene Expression ◽  
Glucose Uptake ◽  
Glucose Transport ◽  
Trichoderma Harzianum ◽  
Glucose Transporter ◽  
Biochemical Characterization ◽  
Carbon Sources ◽  
Low Carbon ◽  
Filamentous Ascomycete

ABSTRACT Using a differential display technique, the gene gtt1, which codes for a high-affinity glucose transporter, has been cloned from the mycoparasite fungus Trichoderma harzianum CECT 2413. The deduced protein sequence of the gtt1 gene shows the 12 transmembrane domains typical of sugar transporters, together with certain residues involved in glucose uptake, such as a conserved arginine between domains IV and V and an aromatic residue (Phe) in the sequence of domain X. The gtt1 gene is transcriptionally regulated, being repressed at high levels of glucose. When carbon sources other than glucose are utilized, gtt1 repression is partially alleviated. Full derepression of gtt1 is obtained when the fungus is grown in the presence of low carbon source concentrations. This regulation pattern correlates with the role of this gene in glucose uptake during carbon starvation. Gene expression is also controlled by pH, so that the gtt1 gene is repressed at pH 6 but not at pH 3, a fact which represents a novel aspect of the influence of pH on the gene expression of transporters. pH also affects glucose transport, since a strongly acidic pH provokes a 40% decrease in glucose transport velocity. Biochemical characterization of the transport shows a very low Km value for glucose (12 μM). A transformant strain that overexpresses the gtt1 gene shows a threefold increase in glucose but not galactose or xylose uptake, a finding which confirms the role of the gtt1 gene in glucose transport. The cloning of the first filamentous ascomycete glucose transporter is the first step in elucidating the mechanisms of glucose uptake and carbon repression in aerobic fungi.

scholarly journals Functional role of sodium glucose transporter in high glucose-mediated angiotensin type 1 receptor downregulation in human proximal tubule cells

2012 ◽  
Vol 303 (5) ◽  
pp. F766-F774 ◽  
Author(s):  
Rekha Yesudas ◽  
Russell Snyder ◽  
Thomas Abbruscato ◽  
Thomas Thekkumkara
Keyword(s):  
Proximal Tubule ◽  
Glucose Uptake ◽  
High Glucose ◽  
Glucose Transporter ◽  
Glucose Transporters ◽  
Ang Ii ◽  
Angiotensin Type ◽  
Human Proximal Tubule

Previously, we have demonstrated human angiotensin type 1 receptor (hAT1R) promoter architecture with regard to the effect of high glucose (25 mM)-mediated transcriptional repression in human proximal tubule epithelial cells (hPTEC; Thomas BE, Thekkumkara TJ. Mol Biol Cell 15: 4347–4355, 2004). In the present study, we investigated the role of glucose transporters in high glucose-mediated hAT1R repression in primary hPTEC. Cells were exposed to normal glucose (5.5 mM) and high glucose (25 mM), followed by determination of hyperglycemia-mediated changes in receptor expression and glucose transporter activity. Exposure of cells to high glucose resulted in downregulation of ANG II binding (4,034 ± 163.3 to 1,360 ± 154.3 dpm/mg protein) and hAT1R mRNA expression (reduced 60.6 ± 4.643%) at 48 h. Under similar conditions, we observed a significant increase in glucose uptake (influx) in cells exposed to hyperglycemia. Our data indicated that the magnitude of glucose influx is concentration and time dependent. In euglycemic cells, inhibiting sodium-glucose cotransporters (SGLTs) with phlorizin and facilitative glucose transporters (GLUTs) with phloretin decreased glucose influx by 28.57 ± 0.9123 and 54.33 ± 1.202%, respectively. However, inhibiting SGLTs in cells under hyperglycemic conditions decreased glucose influx by 53.67 ± 2.906%, while GLUT-mediated glucose uptake remained unaltered (57.67 ± 3.180%). Furthermore, pretreating cells with an SGLT inhibitor reversed high glucose-mediated downregulation of the hAT1R, suggesting an involvement of SGLT in high glucose-mediated hAT1R repression. Our results suggest that in hPTEC, hyperglycemia-induced hAT1R downregulation is largely mediated through SGLT-dependent glucose influx. As ANG II is an important modulator of hPTEC transcellular sodium reabsorption and function, glucose-mediated changes in hAT1R gene expression may participate in the pathogenesis of diabetic renal disease.

scholarly journals Effects of glucose and insulin on glucokinase activity in rat hypothalamus

2007 ◽  
Vol 193 (2) ◽  
pp. 259-267 ◽  
Author(s):  
Carmen Sanz ◽  
Isabel Roncero ◽  
Patricia Vázquez ◽  
M Angeles Navas ◽  
Enrique Blázquez
Keyword(s):  
Enzyme Activities ◽  
Physiological Model ◽  
Ventromedial Hypothalamus ◽  
Glucose Sensing ◽  
Biological Models ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
The Brain ◽  
Hypothalamic Slices

In an attempt to study the role of glucokinase (GK) and the effects of glucose and peptides on GK gene expression and on the activity of this enzyme in the hypothalamus, we used two kinds of biological models: hypothalamic GT1-7 cells and rat hypothalamic slices. The expression of the GK gene in GT1-7 cells was reduced by insulin (INS) and was not modified by different glucose concentrations, while GK enzyme activities were significantly reduced by the different peptides. Interestingly, a distinctive pattern of GK activities between the ventromedial hypothalamus (VMH) and lateral hypothalamus (LH) were found, with higher enzyme activities in the VMH as the glucose concentrations rose, while LH enzyme activities decreased at 2.8 and 20 mM glucose, the latter effect being prevented by incubation with INS. These effects were produced only by d-glucose and the modifications found were due to GK, but not to other hexokinases. In addition, GK activities in the VMH and the LH were reduced by glucagon-like peptide 1, leptin, orexin B, INS, and neuropeptide Y (NPY), but this effect was only statistically significant for NPY in LH. Our results indicate that the effects of both glucose and peptides occur on GK enzyme activities rather than on GK gene transcription. Moreover, the effects of glucose and INS on GK activity suggest that in the brain GK behaves in a manner opposite to that in the liver, which might facilitate its role in glucose sensing. Finally, hypothalamic slices seem to offer a good physiological model to discriminate the effects between different areas.

scholarly journals Genetically Engineered Insulin Mediated by Glucose Transporter-2 (GLUT2) Promoter for the Biosynthesis of Insulin in Rat Hepatocytes: Insulin Gene Therapy

2021 ◽  
Author(s):  
Gehad Abdallah
Keyword(s):  
Gene Therapy ◽  
Pancreatic Beta Cells ◽  
Glucose Transporter ◽  
Glucose Sensing ◽  
Genetically Engineered ◽  
Insulin Gene ◽  
Site Directed Mutagenesis ◽  
Target Cells ◽  
Insulin Production ◽  
Glucose Transporter 2

Abstract Background: Expression of insulin in hepatocytes by hepatic gene therapy is a promising treatment of diabetes. The conversion of immature proinsulin to mature insulin occurs only in cells that contain the enzymes responsible for the cleavage of proinsulin to insulin.Results: I engineered rat proinsulin with the sites of cleavage (Furin Cleavable Sites) using site directed mutagenesis for removal of C-peptide to form the two chains A and B for mature insulin production. This engineered proinsulin was constructed into a non-viral expressing vector and regulated by glucose transporter-2 promoter to control the amount of mature insulin expressed, and to modulate the amount of glucose found in hepatocytes. The mature, active and regulated expressed insulin was secreted according to the amount of glucose regulated by the glucose transporter-2 promoter. Concolusion: For successful hepatic insulin gene therapy, insulin production must be tightly coupled to glucose concentration. Hepatocytes are excellent target cells for insulin gene therapy since, they are similar to pancreatic beta cells, they have the ability to rapidly adapt to blood glucose concentrations as they possess glucose-sensing components, such as Glucose Transporter-2.

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