Altered Islet Function May Promote a Lean Phenotype in Tafazzin Deficient Mice
Bibliographic record
Abstract
Tafazzin is a transacylase that maintains mitochondrial membrane integrity and the function of the mitochondrial respiratory chain. Specifically, tafazzin maintains the content and molecular structure of the unique tetra‐acyl phospholipid cardiolipin (CL) located in the inner mitochondrial membrane. Despite abundant evidence that mitochondrial dysfunction is associated with insulin resistance, little is known about the potential role of CL and tafazzin in the trajectory of this disease. To investigate the in vivo effects of tafazzin deficiency, we have utilized a mouse model with a doxycycline‐ inducible tafazzin shRNA knock‐down. We have previously established that tafazzin knock‐down mice are protected against the development of obesity, and insulin resistance compared to control litter mates. Tafazzin deficiency promotes a lean phenotype due to a coordinated elevation in adipose lipolysis and hepatic fatty acid oxidation. We have now determined that glucagon and insulin levels in the blood and whole islets are significantly reduced with tafazzin deficiency. We have also ascertained that the quantity and function of beta‐cells were similar between genotypes. However, despite similar levels of alpha‐cells, glucagon secretion during high‐glucose conditions was elevated from islets isolated from tafazzin knock‐down mice. As a result, tafazzin knock‐down mice exhibited significantly higher circulating ratios of glucagon to insulin during glucose challenges. Our experiments indicate that tafazzin may have a role in regulating islet function. These data also suggest that mice deficient in tafazzin may be protected in part against weight gain by promoting glucagon secretion during fed states. Since, the development of type 2 diabetes is closely related to obesity and pancreatic function altering cardiolipin synthesis may be a novel therapeutic option for patients at risk for type 2 diabetes. Support or Funding Information Heart and Stroke Foundation of Canada Children's Hospital Research Institute of Manitoba
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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 | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| 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".