Loss of tetraspanin‐7 expression reduces pancreatic β‐cell exocytosis Ca<sup>2+</sup> sensitivity but has limited effect on systemic metabolism
Bibliographic record
Abstract
Abstract Background Tetraspanin‐7 (Tspan7) is an islet autoantigen involved in autoimmune type 1 diabetes and known to regulate β‐cell L‐type Ca 2+ channel activity. However, the role of Tspan7 in pancreatic β‐cell function is not yet fully understood. Methods Histological analyses were conducted using immunostaining. Whole‐body metabolism was tested using glucose tolerance test. Islet hormone secretion was quantified using static batch incubation or dynamic perifusion. β‐cell transmembrane currents, electrical activity and exocytosis were measured using whole‐cell patch‐clamping and capacitance measurements. Gene expression was studied using mRNA‐sequencing and quantitative PCR. Results Tspan7 is expressed in insulin‐containing granules of pancreatic β‐cells and glucagon‐producing α‐cells. Tspan7 knockout mice (Tspan7 y/− mouse) exhibit reduced body weight and ad libitum plasma glucose but normal glucose tolerance. Tspan7 y/− islets have normal insulin content and glucose‐ or tolbutamide‐stimulated insulin secretion. Depolarisation‐triggered Ca 2+ current was enhanced in Tspan7 y/− β‐cells, but β‐cell electrical activity and depolarisation‐evoked exocytosis were unchanged suggesting that exocytosis was less sensitive to Ca 2+ . TSPAN7 knockdown (KD) in human pseudo‐islets led to a significant reduction in insulin secretion stimulated by 20 mM K + . Transcriptomic analyses show that TSPAN7 KD in human pseudo‐islets correlated with changes in genes involved in hormone secretion, apoptosis and ER stress. Consistent with rodent β‐cells, exocytotic Ca 2+ sensitivity was reduced in a human β‐cell line (EndoC‐βH1) following Tspan7 KD. Conclusion Tspan7 is involved in the regulation of Ca 2+ ‐dependent exocytosis in β‐cells. Its function is more significant in human β‐cells than their rodent counterparts.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| 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) | 0.002 | 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 teacher head, 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".