Essentiality of intron control in the induction of c‐ <i>fos</i> by glucose and glucoincretin peptides in INS‐1 β‐cells
Bibliographic record
Abstract
Glucose controls long-term processes in the pancreatic beta-cell such as metabolic enzymes gene expression, cell growth, and apoptosis. Such control is likely mediated via the expression of immediate-early response genes since several of these genes including c-fos are strongly induced by glucose in the beta-cell line INS-1, provided costimulation with cAMP-raising glucoincretin hormones. This study addresses the mechanism of c-fos gene activation by glucose. Glucose in the presence of chlorophenylthio-cAMP generated a low threefold induction of the c-fos/basic luciferase reporter gene, which includes only the c-fos promoter. In contrast, the c-fos/intron construct containing the first intron in addition to promoter elements showed a pronounced 16-fold induction, comparable to the increased c-fos mRNA accumulation. Similar observations were made with glucose in combination with the glucoincretins glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide, and pituitary adenylyl cyclase-activating peptide 38. Deletion of a 119 bp region in intron 1 that includes a transcriptional arrest site did not affect the inductive process. In contrast, a 534 bp deletion comprising a major part of the intron reduced the induction by 75%. At the promoter level, mutating the cAMP response element reduced by more than 60% the transcriptional activation whereas mutating the serum response element had no effect. Inhibitors of protein kinase A and Ca(2+)/calmodulin-dependent protein kinases each reduced by 50% the reporter gene activation and together fully prevented the glucose-glucoincretin effect. In conclusion, the strong induction of c-fos by glucose and glucoincretins results from Ca(2+) and cAMP signaling pathways addressing both the CRE in the promoter and essential response element(s) in the first intron that are unrelated to the transcription arrest site.
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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 | 0.001 | 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 | 0.000 |
| 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".