Regulation of Skeletal Muscle Carbohydrate Metabolism During Mammalian Hibernation
Bibliographic record
Abstract
Thirteen-lined (Ictidomys tridecemlineatus) and Richardson’s (Urocitellus richardsonii) ground squirrels survive harsh winter conditions by entering hibernation, spending the majority of their time in a state of torpor, where metabolic functions are strongly suppressed and reprioritized to ensure long term survival. This thesis analyzed biochemical controls on carbohydrate metabolism during hibernation by characterizing the regulation of crucial enzymes of the glycolytic and gluconeogenic pathways: glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate kinase (PK), and fructose-1,6-bisphosphatase (FBPase). Important signal transduction enzymes regulating carbohydrate metabolism were also evaluated: protein phosphatase 2A (PP2A) and glycogen synthase kinase 3 (GSK3). The state of glycolysis in ground squirrel skeletal muscle was assessed by characterizing the bifunctional enzyme GAPDH and the terminal enzyme PK. Results showed that muscle GAPDH and PK activities were substantially suppressed during torpor. PK suppression was linked to reversible serine/threonine phosphorylation. GAPDH regulation was more complex with activity potentially mediated by one or more posttranslational modifications including acetylation, methylation and phosphorylation, as identified through mass spectrometry and Western blot analyses. The gluconeogenic state of muscle was assessed by characterizing FBPase as well as GAPDH operation in its gluconeogenic direction. In both cases, results indicated reductions in gluconeogenic function during torpor. Suppressed FBPase activity (i.e. decreased Vmax, increased Km F1,6P2) was linked with an increase in FBPase phosphorylation and allosteric controls by AMP and F2,6P2. Analysis of PP2A catalytic subunit showed that elevated phosphorylation at tyrosine307 accompanied a significant increase in Km peptide, indicating reduced activity of PP2A during torpor. This was corroborated by computational analysis of tyrosine307 phosphorylation effects on substrate binding. Skeletal muscle GSK3 activity also decreased during torpor associated with enhanced GSK3 phosphorylation at serine9. However, the principal substrate of GSK3, glycogen synthase, showed increased phosphorylation suggesting that a different protein kinase was responsible for its control during torpor. Taken together these studies suggest that skeletal muscle glycolysis and gluconeogenesis are suppressed during ground squirrel torpor via posttranslational modification and regulation of key enzymes. Reversible controls over glycolytic and gluconeogenic enzymes would allow for the quick reactivation of muscle metabolism to support shivering thermogenesis and a return to normal euthermic function during arousal.
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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 | 0.000 |
| 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 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".