Gene Expression Pattern of PI3K/AKT Pathway Based on Insulin Resistance and Vitamin D Toward the Understanding of T2DM Pathogenesis
Bibliographic record
Abstract
Abstract Background Insulin-stimulated glucose transport occurs via PI3K/AKT-dependent pathway which results in GLUT4 translocation from intracellular vesicles to plasma membrane and glucose uptake. PTEN, as a phosphatase, is the main antagonist of the PI3K/AKT pathway’s kinases. Present study was performed to investigate underlying mechanism responsible for defects in insulin signaling and the plausible role of vitamin D in pathogenesis of T2DM through the comparison of serum vitamin D and expression of genes involved in insulin signaling in diabetics and non-diabetics.Results RT-PCR was employed to investigate mRNA expression level of IRS1/PI3K/PDK1/AKT2/GLUT4/PTEN in diabetic and non-diabetic participants and serum vitamin D was measured by HPLC. Findings provide evidence that IRS1 expression was preserved while PI3K /AKT2/GLUT4 were expressed significantly lower and PDK1 was expressed significantly higher in diabetics compared to non-diabetics. Albeit there was no significant difference in PTEN expression between groups, it was up-regulated by the years of having diabetes. No significant correlation between serum vitamin D and gene expression of GOIs was observed in either group.Conclusion Since PTEN has been identified as a negative regulator of insulin signaling, it has generated great interest in new therapeutic approaches. This study reveals that insulin resistance is not caused through an alteration in PTEN expression as a primary defect but may be caused by decreased PI3K/AKT2/GLUT4 signalling and dysregulation of feedback loops. Particularly, PTEN expression showed a significant relation with duration of diabetes, suggesting that PTEN may not be the cause of the reduced expression of PI3K/AKT pathway in diabetics while it can be the effect of that. Therefore, the future investigations should be focused on regulators of pathway instead of PTEN. No significant correlation between serum vitamin D and gene expression of GOIs could be due to the non-linearity relationships as insulin signaling is a cascade with amplifying properties.
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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 | 0.001 | 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) | 0.001 | 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".