Glucose‐dependent insulinotropic polypeptide signaling in pancreatic β‐cells and adipocytes
Bibliographic record
Abstract
Glucose-dependent insulinotropic polypeptide (GIP) was the first incretin to be identified. In addition to stimulating insulin secretion, GIP plays regulatory roles in the maintenance, growth and survival of pancreatic islets, as well as impacting on adipocyte function. The current review focuses on the intracellular signaling pathways by which GIP contributes to the regulation of β-cell secretion and survival, and adipocyte differentiation and lipogenesis. Studies on signaling underlying the insulinotropic actions of the incretin hormones have largely been carried out with glucagon-like peptide-1. They have provided evidence for contributions by both protein kinase A (PKA) and exchange protein directly activated by cyclic adenosine monophosphate (EPAC2), and their probable role in GIP signaling is discussed. Recent studies have shown that inhibition of the kinase apoptosis signal-regulating kinase 1 (ASK1) by GIP plays a key role in reducing mitochondria-induced apoptosis in β-cells through protein kinase B (PKB)-mediated pathways, and that GIP-induced post-translational modification of voltage- dependent K(+) (Kv) channels also contributes to its prosurvival role. Through regulation of gene expression, GIP tips the balance between pro- and anti-apoptotic members of the B-cell lymphoma-2 (Bcl-2) protein family towards β-cell survival. GIP also plays important roles in the differentiation of pre-adipocytes to adipocytes, and in the regulation of lipoprotein lipase expression and lipogenesis. These events involve interactions between GIP, insulin and resistin signaling pathways. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2012.00196.x, 2012).
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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 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
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".