Novel genes expressed in the pancreatic islets and regulated by IGF-I
Bibliographic record
Abstract
Insulin-like growth factor (IGF)-I is mainly produced by hepatocytes and other tissues including pancreas at lower level.Acting through its receptor, IGF-IR, it promotes embryonic development, postnatal growth and maturation of major organ systems.To evaluate the effects of increased IGF-I level on islet growth and glucose homeostasis, our lab previously characterized MT-IGF mice which over express IGF-I gene under the metallothionine I promoter and found that its expression was highly concentrated to -cells.IGF-I overexpression led to a significant hypoglycemia in fasted animals, hypoinsulinemia and improved glucose tolerance.Moreover, MT-IGF-I mice were significantly resistance to streptozotocin-induced diabetes, with diminished hyperglycemia and abolished weight loss and reduce mortality.Although IGF-I is known to stimulate protein synthesis, cell survival and proliferation, the specific target within the islets have not been screened in a systematic manner.In order to explore novel targets of IGF-I action, we performed a whole genome DNA microarray analysis on isolated islets from overexpressing IGF-I mice, and found 82 genes specifically up-or down-regulated.Prominent targets among those are HSD11B1 encoding 11 -hydroxysteroid dehydrogenase-1 (11 -HSD1) and CCN5/Wisp-2, previously not shown to be expressed in the pancreatic islets and regulated by IGF-I.In this study, we further checked 1) the localization of these targets in pancreatic islets both at the mRNA and protein level; 2) the effect of CCN5/Wisp2 in pancreatic islet proliferation and survival; 3) the effect of 11 -HSD1 under IGF-I regulation and assessed its functional relevance to type 2 diabetes.xxi Claim of OriginalityThis doctoral thesis provides important information regarding the role of novel IGF-I targets in pancreatic islets.These targets can be important for islet proliferation and survival 1) To identify the novel target of IGF-I we performed whole genome DNA microarray analysis on RNA extracted from IGF-I over expressing mice and found 82 genes which can be potential candidate for β-cell proliferation and survival.None of these targets were shown to be regulated by IGF-I before in pancreatic islet cells.2) We identified CCN5 for the first time in islet β-cells in higher level compare to WT mice.CCN5 expression in increased level contributes to islet cell growth and/or survival.3) We also found the decreased expression of 11β-HSD1 in α-cell due to overexpression of IGF-1 in pancreatic islet.Decreased expression of 11β-HSD1 may cause increased basal insulin secretion in MT-IGF mice.This may also contribute to islet survival.xxii
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 |
| 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) | 0.001 | 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".