A general and islet cell-enriched overexpression of IGF-I results in normal islet cell growth, hypoglycemia, and significant resistance to experimental diabetes
Bibliographic record
Abstract
Insulin-like growth factor I (IGF-I) is normally produced from hepatocytes and various other cells and tissues, including the pancreas, and is known to stimulate islet cell replication in vitro, prevent Fas-mediated beta-cell destruction and delay the onset of diabetes in nonobese diabetic mice. Recently, however, the notion that IGF-I stimulates islet cell growth has been challenged by the results of IGF-I and receptor gene targeting. To test the effects of a general, more profound increase in circulating IGF-I on islet cell growth and glucose homeostasis, we have characterized MT-IGF mice, which overexpress the IGF-I gene under the metallothionein I promoter. In early reports, a 1.5-fold-elevated serum IGF-I level caused accelerated somatic growth and pancreatic enlargement. We demonstrated that the transgene expression, although widespread, was highly concentrated in the beta-cells of the pancreatic islets. Yet, islet cell percent and pancreatic morphology were unaffected. IGF-I overexpression resulted in significant hypoglycemia, hypoinsulinemia, and improved glucose tolerance but normal insulin secretion and sensitivity. Pyruvate tolerance test indicated significantly suppressed hepatic gluconeogenesis, which might explain the severe hypoglycemia after fasting. Finally, due to a partial prevention of beta-cell death against onset of diabetes and/or the insulin-like effects of IGF-I overexpression, MT-IGF mice (which overexpress the IGF-I gene under the metallothionein I promoter) were significantly resistant to streptozotocin-induced diabetes, with diminished hyperglycemia and prevention of weight loss and death. Although IGF-I might not promote islet cell growth, its overexpression is clearly antidiabetic by improving islet cell survival and/or providing insulin-like effects.
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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 | 0.000 |
| 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".