Decreased In Situ Insulin Receptor Dephosphorylation in Hyperglycemia-Induced Insulin Resistance in Rat Adipocytes
Bibliographic record
Abstract
The regulation of insulin receptor (IR) tyrosine (tyr) phosphorylation is a key step in the control of insulin signaling. Augmented IR tyr dephosphorylation by protein tyrosine phosphatases (PTPs) may contribute to insulin resistance. To investigate this possibility in hyperglycemia-induced insulin resistance, primary cultured rat adipocytes were rendered insulin-resistant by chronic exposure (18 h) to 15 mmo/l glucose combined with 10(-7) mol/l insulin. Insulin-resistant adipocytes showed a decrease in insulin sensitivity and a maximum response of 2-deoxyglucose uptake, which was associated with a decrease in maximum insulin-stimulated IR tyr phosphorylation in situ. To assess tyr dephosphorylation, IRs of insulin-stimulated permeabilized adipocytes were labeled with [gamma-32P]ATP and chased for 2 min with unlabeled ATP in the presence of EDTA. In a nonradioactive protocol, insulin-stimulated adipocytes were permeabilized and exposed to EDTA and erbstatin for 2 min, and IRs were immunoblotted with anti-phosphotyrosine (pY) antibodies. Both methods showed a similar diminished extent of IR tyr dephosphorylation in resistant cells. Immunoblotting of four candidate IR-PTPs demonstrated no change in PTP1B or the SH2 domain containing phosphatase-2 (SHP-2), whereas a significant decrease in leukocyte antigen-related phosphatase (LAR) (51 +/- 3% of control) and an increase in PTP-alpha (165 +/- 16%) were found. Activity of immunoprecipitated PTPs toward a triple tyr phosphorylated IR peptide revealed a correlation with protein content for PTP1B, SHP-2, and LAR but a decrease in apparent specific activity of PTP-alpha. The data indicate that decreased IR tyr phosphorylation in hyperglycemia-induced insulin resistance is not due to enhanced dephosphorylation. The diminished IR tyr dephosphorylation observed in this model is associated with decreased LAR protein content and activity.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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".