Dual Regulation of Glucose Homeostasis by the Adaptor Proteins Nck
Bibliographic record
Abstract
Nck1 and Nck2 adaptor proteins mediate intracellular signaling from activated plasma membrane receptor tyrosine kinases. Previous studies reported that the Nck expression levels vary with insulin sensitivity, suggesting a role for Nck in regulating insulin signaling. We previously showed that Nck1 −/− mice fed a high fat diet (HFD) display better glucose disposal ability and hepatic insulin signaling compared with HFD insulin resistant Nck1 +/+ littermates. In fact, we found that Nck1 interacts with and mediates signaling from IRE1α, an important component of the Unfolded Protein Response that inhibits insulin signaling by inducing JNK‐dependent phosphorylation of the insulin receptor substrate 1 (IRS‐1) on an inhibitory site. In contrast, we observed that Nck2 −/− mice fed a normal chow diet (NCD) or a high fat diet (HFD) display greater glucose intolerance and insulin resistance compared to Nck2 +/+ littermates mice. In agreement, we found decreased insulin‐induced hepatic Akt phosphorylation/activation in NCD Nck2 −/− mice compared with their littermate controls. All together, our data provide strong evidence that the two Nck adaptors have distinct role in modulating insulin signaling in vivo . Further studies are in progress to define the mechanisms by which Nck differentially regulate glucose homeostasis. Work supported by CIHR and CDA. JD holds a FRSQ postdoctoral fellowship.
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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 | 0.001 |
| 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".