The Role of PPAR‐g in Shp1‐Mediated Regulation of Glucose Homeostasis in the Liver
Bibliographic record
Abstract
The protein‐tyrosine phosphatase Shp1 plays a central role in high‐fat diet (HFD)‐induced insulin resistance. This enzyme, which negatively regulates insulin action on glucose homeostasis, is upregulated in metabolic tissues, such as liver, muscle and adipose tissue, of mice submitted to HFD. Hepatocyte‐specific Shp1 knockout mice (Ptpn6 H‐KO ) submitted to HFD develop hepatic steatosis but show less hepatic insulin resistance. These effects might be due to the observed attenuation of HFD‐induced inflammation and liver damage. Moreover, while Ptpn6 H‐KO mice present a significant increase in PPARg expression, overexpression of Shp1 reduces the activity of this nuclear receptor. The aim of the present study is to evaluate the role of PPARg on the amelioration of liver inflammation in HFD‐fed Ptpn6 H‐KO mice. For this, male Ptpn6 H‐KO mice were kept on standard diet (SD) or HFD for 18 weeks. During the last 4 weeks the animals were treated with a very low dose of rosiglitazone, a known PPARg agonist. Rosiglitazone‐treated Ptpn6 H‐KO mice showed an improvement in glucose tolerance without a significant change in insulinemia during oral glucose tolerance test. Insulin‐induced Akt phosphorylation, was increased by rosiglitazone in the Ptpn6 H‐KO mice, which may partially explain the amelioration in glucose tolerance. Despite the fact that rosiglitazone increased hepatic steatosis in Ptpn6 H‐KO mice, the drug also augmented the levels of the anti‐inflammatory cytokine, IL‐10. However, rosiglitazone did not improve the pattern of pro‐inflammatory cytokines in the liver. Altogether, our data support that Shp1 effects on glucose homeostasis involve the activation of PPARg, but the complete role of these players on liver inflammation has yet to be elucidated. Support or Funding Information Canadian Institutes of Health Research and CNPq
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 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".