In vivo imaging of GLUT4 translocationThis paper is one of a selection of papers published in this Special Issue, entitled 14th International Biochemistry of Exercise Conference – Muscles as Molecular and Metabolic Machines, and has undergone the Journal’s usual peer review process.
Bibliographic record
Abstract
In skeletal muscle, both insulin and muscle contractions mediate translocation of glucose transporter GLUT4 to the plasma membrane proper, the sarcolemma, and the specialized membrane channel network, the transverse (t)-tubules. Despite the fact that skeletal muscle glucose uptake plays a major role in normal conditions, in insulin resistance, and type II diabetes, the details of GLUT4 translocation and the intracellular signalling involved have not been fully described. A main reason is that the majority of experiments have been carried out in muscle cultures in vitro. In vitro cultured muscle is not fully differentiated and, therefore, diverges from real muscle, in that it has lower expression of GLUT4, an underdeveloped or nonexistent t-tubule network, and a reduced or nonexistent response to insulin. Thus, experiments carried out in cultured muscle cell systems might give misleading results on how GLUT4 translocation and the signalling involved takes place. To address this problem, a confocal imaging technique has been developed that allows delineation of the spartial and spatial distribution of GFP-tagged GLUT4 (GLUT4-GFP) translocation in living muscle fibers in situ in anesthetized mice. The effects of stimuli with insulin or in situ muscle contractions in fully differentiated muscle fibers can now be studied before, during, and after applying stimuli. Initial analysis of insulin-stimulated GLUT4-GFP translocation showed a delay in maximal translocation between the sarcolemma and t-tubules. Corresponding to the delay, we found that fluorescent tagged insulin reaches the sarcolemma first and then, with a delay, diffuses into the t-tubule system, enabling interaction with local insulin receptors and, in turn, triggering local insulin signalling and local GLUT4 translocation. In parallel, we showed that the majority of GLUT4 depot vesicles do not move long distances but are depleted locally in the sarcolemma or t-tubule regions. Analysis of GLUT4 translocation in insulin-resistant muscle showed that, primarily, GLUT4 recruitment in the t-tubule region is affected. We have now analysed the kinetics of contraction-mediated GLUT4 translocation and reinternalization, as well as dilineated some of the key signalling points involved in these processes.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".