Bibliographic record
Abstract
This thesis examined the roles of interleukin (IL)-6 in the regulation of glucose homeostasis, with a specific focus on skeletal muscle. Study 1 sought to determine whether muscle glycogen content is a stimulus for the production of IL-6, examining the periods during and after exercise. The relationship between IL-6 and muscle glycogen content was measured during similar bouts of exhaustive exercise on 2 occasions that resulted in large increases in muscle messenger (m)RNA for IL-6 and circulating levels of IL-6. On 1 occasion, subjects received carbohydrate during recovery to facilitate rates of glycogen resynthesis. During exercise, subjects performed similar bouts of exercise, such that differences in an individual’s glycogen levels between trials could be compared with differences in IL-6. No correlation was detected between the net change in glycogen content and the net change in plasma IL-6 or IL-6 mRNA from rest to exhaustion. Moreover, when the difference within subjects at exhaustion in IL-6 and glycogen was compared, there was no correlation between the 2 variables. During recovery, although carbohydrate intake significantly increased glycogen resynthesis, there was no change in postexercise IL-6 mRNA level or plasma IL-6 concentration. Therefore, glycogen was not the sole regulator of IL-6 production in skeletal muscle. Study 2 examined the direct effect of IL-6 and tumor necrosis factor (TNF)-α on glucose transport and the phosphorylation of key signalling proteins with or without insulin and during rodent muscle contraction. Under basal conditions, IL-6 increased glucose transport in association with an increase in 5′AMP-activated protein kinase (AMPK) and AS160 phosphorylation, but IL-6 decreased insulin-stimulated glucose transport via a reduction in phosphorylation of calcium–calmodulin-dependent protein kinase (CaMK)II and AS160. A novel finding generated from these experiments was the direct involvement of IL-6 in contraction-mediated glucose transport. In the case of muscle contraction, IL-6 was found to increase the phosphorylation of CaMKII and AS160. This research suggests that the activation of CaMKII is involved in the actions of IL-6 under insulin-stimulated and contraction-mediated conditions. Furthermore, AS160 was identified as a common signalling intermediate, influenced by IL-6. It also suggests that AS160 may be a point of convergence for multiple signalling pathways. Finally, the actions of TNF-α mimicked those of IL-6, except during contraction, where TNF-α had no significant effect on glucose transport and attenuated the effects of IL-6.
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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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".