Glucose is a key metabolic regulator of osteoclasts; glucose stimulated increases in ATP/ADP ratio and calmodulin kinase II activity
Bibliographic record
Abstract
Glucose-stimulated increases in osteoclast activity are mediated, at least in part, by transcriptional regulation of H+-ATPase expression through a mechanism involving p38 mitogen-activated protein kinase. We hypothesized that early events in the glucose-dependent signaling pathway would be similar to those identified in other glucose-sensitive cells, such as islet beta-cells, including rapid changes in the cellular ATP/ADP ratio and mobilization of intracellular Ca2+. We demonstrate that glucose stimulates a prolonged 50% increase in the ATP/ADP ratio that was maximal 30 s after glucose concentrations were increased. Glucose stimulated a transient 30% increase in calcium/calmodulin-dependent kinase II (CaMK II) activity that was maximal 3 min after the glucose concentration was increased. CaMK II was activated maximally by 3 mmol D-glucose/L in 3-min assays. Activation of CaMK II in the presence of the nonmetabolizable glucose analog 2-deoxyglucose was 2-fold greater than with D-glucose but was unchanged by glucosamine. Pretreatment of osteoclasts with the intracellular Ca2+ chelator BAPTA-AM inhibited glucose transport by 75%. BAPTA-AM treatment also prevented glucose-dependent stimulation of CaMK II. The data indicate that osteoclasts utilize a glucose-sensing mechanism similar to that of beta-cells and that glucose-stimulated signaling in osteoclasts involves changes in the ATP/ADP ratio and mobilization of intracellular Ca2+, resulting in activation of CaMK II.
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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".