Restoration of Lepr in β cells of Lepr null mice does not prevent hyperinsulinemia and hyperglycemia
Bibliographic record
Abstract
Objective The adipose-derived hormone leptin plays an important role in regulating body weight and glucose homeostasis. Leptin receptors are expressed in the central nervous system as well as peripheral tissues involved in regulating glucose homeostasis, including insulin-producing β cells of the pancreas. Previous studies assessing the role of leptin receptors in β cells used Cre- loxP to disrupt the leptin receptor gene ( Lepr ) in β cells, but variable results were obtained. Furthermore, recombination of Lepr was observed in the hypothalamus or exocrine pancreas, in addition to the β cells, and Lepr in non-β cells may have compensated for the loss of Lepr in β cells, thus making it difficult to assess the direct effects of Lepr in β cells. To determine the significance of Lepr exclusively in β cells, we chose to selectively restore Lepr in β cells of Lepr null mice ( Lepr loxTB/loxTB ). Materials and methods We used a mouse model in which endogenous expression of Lepr was disrupted by a loxP -flanked transcription blocker ( Lepr loxTB/loxTB ), but was restored by Cre recombinase knocked into the Ins1 gene, which is specifically expressed in β cells ( Ins1 Cre). We bred Lepr loxTB/loxTB and Ins1 Cre mice to generate Lepr loxTB/loxTB and Lepr loxTB/loxTB Ins1 Cre mice, as well as Lepr wt/wt and Lepr wt/wt Ins1 Cre littermate mice. Male and female mice were weighed weekly between 6 and 11 weeks of age and fasting blood glucose was measured during this time. Oral glucose was administered to mice aged 7–12 weeks to assess glucose tolerance and insulin secretion. Relative β and α cell area and islet size were also assessed by immunostaining and analysis of pancreas sections of 12–14 week old mice. Results Male and female Lepr loxTB/loxTB mice, lacking whole-body expression of Lepr , had a phenotype similar to db/db mice characterized by obesity, hyperinsulinemia, glucose intolerance, and impaired glucose stimulated insulin secretion. Despite restoring Lepr in β cells of Lepr loxTB/loxTB mice, fasting insulin levels, blood glucose levels and body weight were comparable between Lepr loxTB/loxTB Ins1 Cre mice and Lepr loxTB/loxTB littermates. Furthermore, glucose tolerance and insulin secretion in male and female Lepr loxTB/loxTB Ins1 Cre mice were similar to that observed in Lepr loxTB/loxTB mice. Analysis of pancreatic insulin positive area revealed that restoration of Lepr in β cells of Lepr loxTB/loxTB mice did not prevent hyperplasia of insulin positive cells nor did it rescue Glut-2 expression. Conclusion Collectively, these data suggest that direct action of leptin on β cells is insufficient to restore normal insulin secretion and glucose tolerance in mice without leptin receptor signaling elsewhere.
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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".