Bibliographic record
Abstract
Following the binding of insulin to its cell surface receptor there is rapid activation of the insulin receptor kinase (IRK), leading to autophosphorylation of the receptor on tyrosine residues and the capacity to tyrosine phosphorylate various cellular substrates. The peroxovanadium compounds (pVs) were shown to activate the IRK in the complete absence of insulin and correlatively activate the full insulin signalling cascade. Along with earlier studies on mutant IRKs, this observation indicated that IRK function is both necessary and sufficient for insulin signaling. IRK is rapidly internalized into the endosomal apparatus (ENs), where it remains activated for a significant time and is capable of entraining insulin signalling events. Thus, modulation of the IRK in ENs is an important means by which insulin signalling is influenced. In recent years, several endosomal processes were shown to regulate IRK activity. The presence in ENs of a relatively specific insulin protease (endosomal acidic insulinase (EAI)) is responsible for limiting ligand availability in this compartment. Also, studies of the mechanism of pV’s ability to activate IRK have identified an IRK-associated PTP (IRK-aPTP) which functions to dephosphorylate and inactivate the activated IRK. Thus, both EAI and IRK-aPTP limit the duration and extent of IRK activation and signalling. Inhibition of IRK-aPTP results in activation of the IRK and the full insulin response. Inhibition of EAI has also been shown to augment IRK activity and signalling. Therefore, EAI and IRK-aPTP are suitable therapeutic targets against which drug development should lead to clinically important agents for treating insulin resistance.
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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 | 0.001 | 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) | 0.004 | 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".