A Transgenic Mouse Model to Study Glucose Transporter 4myc Regulation in Skeletal Muscle
Bibliographic record
Abstract
Skeletal muscle is the major site for dietary glucose disposal, taking up glucose via glucose transporter 4 (GLUT4). Although subcellular fractionation studies demonstrate that insulin increases GLUT4 density in sarcolemma and transverse tubules, fractionation cannot discern GLUT4 vesicle-membrane association from insertion and exofacial exposure. Clonal muscle cultures expressing exofacially tagged GLUT4 have allowed quantification of GLUT4 exposure at the cell surface, its exocytosis, endocytosis, and partner proteins. We hypothesized that transgenic expression of GLUT4myc in skeletal muscles would provide a useful model to investigate GLUT4 biology in vivo. A homozygous mouse colony was generated expressing GLUT4myc driven by the muscle creatine kinase (MCK) promoter. GLUT4 protein levels were about 3-fold higher in hindlimb muscles of MCK-GLUT4myc transgenic mice compared with littermates (P < 0.05). Insulin (12 nm, 30 min) induced a 2.1-fold increase in surface GLUT4myc detected by immunofluorescence of the exofacial myc epitope in nonpermeabilized muscle fiber bundles (P < 0.05). Glucose uptake and surface GLUT4myc levels were 3.5- and 3-fold higher, respectively, in giant membrane vesicles blebbed from hindlimb muscles of insulin-stimulated transgenic mice compared with unstimulated counterparts (P < 0.05). Muscle contraction also elevated both parameters, an effect partially additive to insulin's. GLUT4myc immunoprecipitation with anti-myc antibodies avoids interfering with associated intracellular binding proteins. Tether, containing a UBX domain, for GLUT4 coimmunoprecipitated with GLUT4myc and insulin stimulation significantly decreased such association (P < 0.05). MCK-GLUT4myc transgenic mice are thus useful to quantify exofacial GLUT4 exposure at the sarcolemma and GLUT4 binding partners in skeletal muscle, essential elements in the investigation of muscle GLUT4 regulation in physiological and pathological states in vivo.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".