Human IGF Binding Protein-3 Overexpression Impairs Glucose Regulation in Mice via an Inhibition of Insulin Secretion
Bibliographic record
Abstract
Human IGF binding protein-3 (hIGFBP-3) overexpression in mice causes hyperglycemia, but its effect on β-cell function is unknown. We compared wild-type mice with mice overexpressing hIGFBP-3 [phoshoglycerate kinase (PGK)BP3] and mutant (Gly⁵⁶/Gly⁸⁰/Gly⁸¹)hIGFBP-3 devoid of IGF binding affinity (PGKmBP3). Intraperitoneal glucose and insulin tolerance tests were performed, and glucose, IGFBP-3, IGF-I, and insulin were determined. Pancreatic sections were used for islet histomorphometry and stained with antibodies against insulin, glucagon, and hIGFBP-3. Pancreatic islets were isolated to determine the expression of IGFBP-3, and glucose-stimulated insulin secretion was measured using both islet batch incubation and perifusion. IGFBP-3 was expressed in β-cells but not in other islet cell types. Fasting glucose concentration was elevated in PGKBP3 mice (6.27 ± 0.31 mm) compared with PGKmBP3 mice (3.98 ± 0.36 mm) and wild-type mice (4.84 ± 0.07 mm). During glucose tolerance test, glucose declined more slowly in PGKBP3 and PGKmBP3 mice than in wild-type mice, and insulin secretion was impaired in PGKBP3 mice. During insulin tolerance test, insulin declined more slowly in both transgenic mice compared with wild-type mice. Insulin secretion in islets incubated with 3.3 mm glucose was similar among groups, but islet insulin response to 16.7 mm glucose alone, or with carbachol and cAMP enhancers, was reduced in PGKBP3 and PGKmBP3 mice compared with wild-type controls. ATP content, Akt phosphorylation, and phosphoglucose isomerase activity were reduced in islets from both transgenic mice. Thus, overexpression of hIGFBP-3 in mice delays in vivo insulin clearance and reduces glucose-stimulated insulin secretion in pancreatic islets by both IGF-dependent and IGF-independent mechanisms.
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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) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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".