Mechanisms regulating GLUT4 transcription in skeletal muscle cells are highly conserved across vertebrates

The glucose transporter 4 (GLUT4) plays a key role in glucose uptake in insulin target tissues. This transporter has been extensively studied in many species in terms of its function, expression and cellular traffic and complex mechanisms are involved in its regulation at many different levels. However, studies investigating the transcription of the GLUT4 gene and its regulation are scarce. In this study, we have identified the GLUT4 gene in a teleost fish, the Fugu (Takifugu rubripes), and have cloned and characterized a functional promoter of this gene for the first time in a non-mammalian vertebrate. In silico analysis of the Fugu GLUT4 promoter identified potential binding sites for transcription factors such as SP1, C/EBP, MEF2, KLF, SREBP-1c and GC-boxes, as well as a CpG island, but failed to identify a TATA box. In vitro analysis revealed three transcription start sites, with the main residing 307 bp upstream of the ATG codon. Deletion analysis determined that the core promoter was located between nucleotides -132/+94. By transfecting a variety of 5´deletion constructs into L6 muscle cells we have determined that Fugu GLUT4 promoter transcription is regulated by insulin, PG-J2, a PPARγ agonist, and electrical pulse stimulation. Furthermore, our results suggest the implication of motifs such as PPARγ/RXR and HIF-1α in the regulation of Fugu GLUT4 promoter activity by PPARγ and contractile activity, respectively. These data suggest that the characteristics and regulation of the GLUT4 promoter have been remarkably conserved during the evolution from fish to mammals, further evidencing the important role of GLUT4 in metabolic regulation in vertebrates

Structural and Functional Evolution of Glucose Transporter 4 (GLUT4): A Look at GLUT4 in Fish

The insulin-responsive glucose transporter GLUT4 was first described in 1988 as a result of studies on the regulation of glucose metabolism by insulin [1]. Soon after the discovery of GLUT4, several groups cloned GLUT4 in the human [2], rat [3,4] and mouse [5]. Since its discovery, GLUT4 has received, together with GLUT1, more experimental attention than any other single membrane transport protein. Structurally, GLUT4 follows the predicted model for class I glucose transporters. GLUT4 has a high affinity for glucose, with a Km of approximately 5 mM [6], and also transports mannose, galactose, dehydroascorbic acid and glucosamine [7-10]. In mammals, GLUT4 is mainly expressed in cardiac and skeletal muscle, brown and white adipose tissue, and brain [6,11,12]. GLUT4 plays a pivotal role in whole body glucose homeostasis, mediating the uptake of glucose regulated by insulin [13,14]. GLUT4 is responsible for the reduction in the postprandial rise in plasma glucose levels [6]. Insulin acts by stimulating the translocation of specific GLUT4-containing vesicles from intracellular stores to the plasma membrane (PM) resulting in an immediate increase in glucose transport [6,15]. The disruption of GLUT4 expression has been extensively associated with pathologies of impaired glucose uptake and insulin resistance such as type 2 diabetes and obesity [13,16-18]..

Influencia de las variables de hilatura en la estructura fina del poliéster.

Una microfibra de poliéster (0,9 dtex) ha sido hilada en una continua de anillos variando las condiciones del proceso (velocidad del cursor, tipo de cursor, antibalón, mudada, estiraje) según el método Taguchi. De los hilados obtenidos se han determinado parámetros relacionados con la estructura fina del poliéster (tiempo critico de disolución, solubilidad diferencial y sorción de iodo). También se ha determinado el contenido de oligómeros superficiales.Polyester microfibre (0.9 dtex) has been spun in a ring spinning frame varying the process conditions (speed of traveller, type of traveller, separator, doffing, drawing) according to Taguchi's method. Of the resulting yarns, the following parameters related to the fine structure of polyester have been measured: critical dissolution time, differential solubility and iodine sorption. The content of superficial oligomers has also been determined.Une microfibre de polyester (0,9 dtex) a été fijée en continnue à anneaux en variant les conditions du procédé (vitesse curseur, type de curseur, antiballon, levée, étirage) selon le procédé Taguchi. On a pu déterminer des caractéristiques liées à la structure fine du polyester (durée critique de dissolution, solubilité différentielle et sorption d'iode), ainsi que le contenu d'oligomeres superficiels.Peer Reviewe

GLUT2-mediated glucose uptake and availability are required for embryonic brain development in zebrafish

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

Zebrafish ankrd1a as a common player in heart regeneration and skeletal muscle repair

In contrast to humans, zebrafish have a remarkable ability to regenerate their hearts after injury, while both humans and zebrafish efficiently repair the wounded skeletal muscle. Common players in these two processes might represent potential targets for the development of efficient therapies to stimulate human heart to regenerate after injury. We identified ankrd1a expression to be upregulated in both regenerating zebrafish hearts and in repairing skeletal muscle. Its mammalian homolog ANKRD1/CARP encodes a stress responsive cardiac ankyrin repeat protein involved in transcriptional regulation, sarcomere assembly and mechanosensing. Using a TgBAC(ankrd1a:EGFP) line, we showed that activation of ankrd1a in cryoinjured heart is restricted to border zone cardiomyocytes, implicating this gene in dedifferentiation and proliferation of regenerating cardiomyocytes. After stab wound injury of skeletal muscle expression of the fluorescent reporter was observed from 3 dpi, when new EGFP-positive muscle cells emerged inside the injury zone. At later time points, EGFP-positive myofibers were visible in the deeper tissue layers, concomitant with active repair of the injured tissue. In cryoinjured skeletal muscle, strong activation of ankrd1a was also observed in myofibers adjacent to the injury, and in those on uninjured side. Detection of the transgene in both newly formed myofibers that invade the wound and in the apparently uninjured tissue surrounding the injury suggests the role of ankrd1a in skeletal muscle tissue repair and adaptive processes in uninjured myofibers surrounding the injury site. Our results implicate ankrd1a in zebrafish muscle regeneration, repair and remodeling, promoting it as an attractive target for translational studies, as a player in muscle healing and as a sensor of stressed muscle.10th Strategic Conference of Zebrafish Investigators, January 6-9, 2024 at the Asilomar Conference Grounds in Pacific Grove, Californi

Evaluation of long-term changes in precipitation over Bolivia based on observations and Coupled Model Intercomparison Project models

Using observations and model simulations from the 5th and 6th phases of the Coupled Model Intercomparison Project (CMIP5 and CMIP6, respectively), this study evaluated changes in monthly, seasonal, and annual precipitation over Bolivia from 1950 to 2019. Results demonstrate that observed precipitation is characterized by strong interannual and decadal variability. However, long-term precipitation trends were not identified on the annual scale. Similarly, changes in seasonal precipitation were almost nonsignificant (p > .05) for the study period. Spatially, albeit with its complex orography, no substantial regional variations in observed precipitation trends can be identified across Bolivia. In contrast, long-term precipitation trends, based on CMIP5 and CMIP6 models, suggest a dominance of negative trends, mainly during austral winter (JJA) (−10%) and spring (SON) (−15%). These negative trends were more pronounced in the lowlands of Bolivia (−20%). Overall, these contradictory results highlight the need for validating precipitation trend outputs from model simulations, especially in areas of complex topography like Bolivia.This work was sup-ported by the research projects CGL2017-82216-R,PCI2019-103631, and PID2019-108589RA-I00, financedby the Spanish Ministry of Science and FEDER, theCROSSDRO project financed by the AXIS (Assessment ofCross(X)-sectorial climate impacts and pathways for Sus-tainable transformation), the JPI-Climate co-funded callof the European Commission, and the LINCGLOBAL-CSIC project (INCGLO0023, RED-CLIMA)

Assessment of vapor pressure deficit variability and trends in Spain and possible connections with soil moisture

The Vapor Pressure Deficit (VPD) is one of the most relevant surface meteorological variables; with important implications in ecology, hydrology, and atmosphere. By understanding the processes involved in the variability and trend of the VPD, it is possible to assess the possible impacts and implications related to both physical and human environments, like plant function, water use efficiency, net ecosystem production, atmospheric CO2 growth rate, etc. This study analysed recent temporal variability and trends in VPD in Spain between 1980 and 2020 using a recently developed high-quality dataset. Also, the connection between VPD and soil moisture and other key climate variables (e.g. air temperature, precipitation, and relative humidity) was assessed on different time scales varying from weekly to annual. The objective was to determine if changes in land-atmosphere feedbacks connected with soil moisture and evapotranspiration anomalies have been relevant to assess the interannual variability and trends in VPD. Results demonstrate that VPD exhibited a clear seasonality and dominant positive trends on both the seasonal (mainly spring and summer) and annual scales. Rather, trends were statistically non-significant (p > 0.05) during winter and autumn. Spatially, VPD positive trends were more pronounced in southern and eastern of Spain. Also, results suggest that recent trends of VPD shows low contribution of variables that drive land-atmosphere feedbacks (e.g. evapotranspiration, and soil moisture) in comparison to the role of global warming processes. Notably, the variability of VPD seems to be less coupled with soil moisture variability during summertime, while it is better interrelated during winter, indicating that VPD variability would be mostly related to climate variability mechanisms that control temperature and relative humidity than to land-atmosohere feedbacks. Overall, our findings highlight the importance of assessing driving forces and physical mechanisms that control VPD variability using high-quality climate datasets, especially, in semiarid and sub-humid regions of the world

Tuberculosis causes highly conserved metabolic changes in human patients, mycobacteria‑infected mice and zebrafish larvae

Solid state NMR/Biophysical Organic ChemistryAnimal science

Neuropilin 1 mediates epicardial activation and revascularization in the regenerating zebrafish heart

Unlike adult mammals, zebrafish can regenerate their heart. A key mechanism for regeneration is the activation of the epicardium, leading to the establishment of a supporting scaffold for new cardiomyocytes, angiogenesis and cytokine secretion. Neuropilins are co-receptors mediating signaling of kinase receptors for cytokines known to play critical roles in zebrafish heart regeneration. We investigated the role of neuropilins in response to cardiac injury and heart regeneration. All four neuropilin isoforms nrp1a, nrp1b, nrp2a and nrp2b were upregulated by the activated epicardium and a nrp1a knockout mutant showed a significant delay in heart regeneration and displayed persistent collagen deposition. The regenerating hearts of nrp1a mutants were less vascularized and epicardial-derived cell migration and re-expression of the developmental gene wt1b was impaired. Moreover, cryoinjury-induced activation and migration of epicardial cells in heart explants was reduced in nrp1a mutant. These results identify a key role for Nrp1 in zebrafish heart regeneration, mediated through epicardial activation, migration and revascularization