Protein kinase‐D1 overexpression in mice prevents lipid‐induced insulin resistance and cardiomyopathy by upregulation of glucose uptake
Bibliographic record
Abstract
Disturbances in metabolic substrate uptake promote the development of cardiomyopathy and eventually lead to heart failure. Understanding the pathways that control substrate uptake could enable therapeutic approaches to prevent maladaptive cardiac remodeling. We identified protein kinase‐D1 (PKD1) as a contraction‐activated kinase, which promotes GLUT4‐mediated glucose uptake, without affecting long chain fatty acids (LCFA) uptake. This corroborated with in‐vitro experimentation using PKD1 siRNA in HL‐1 cells and in‐vivo by microPET scan results showing a higher glucose uptake in the hearts of mice overexpressing constitutively active PKD1 (caPKD1). The increased glucose uptake in the heart of caPKD1 mice results in dilated cardiac hypertrophy and heart failure. In contrast, mice on a high fat diet with lipid‐overloaded hearts displayed concentric cardiac hypertrophy, accompanied by insulin resistance. However, hearts of caPKD1 mice on a high fat diet displayed neither dilated nor concentric hypertrophy. Further, these hearts did not show increased glucose uptake nor increased LCFA uptake, demonstrating the role of PKD1 to balance cardiac substrate utilization, which is crucial in preventing pathological cardiomyopathy. In conclusion, in the lipid‐overloaded heart, upregulation of PKD1 offers protection against the development of insulin resistance and hypertrophic remodeling. Grant Funding Source : NWO (Dutch Organisation for scientific research)
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.002 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 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".