Identification of Differentially Expressed Genes and Processes in Myocardial Tissue of Liver-Specific Gck Knockout Mice
Bibliographic record
Abstract
<title>Abstract</title> Background: Diabetic cardiomyopathy is a ventricular disease caused by diabetes mellitus. Abnormalities in the function of the glucokinase (GCK) play an important role in the development of diabetes. The present study is aimed at exploring changes in gene expression and related molecular mechanisms of diabetic myocardial injury in Gck knockout mice. Methods: Liver-specific glucokinase gene knockout mice( Gck w/- ) and wide type ( Gck w/w )mice generated using the Cre-loxP gene targeting strategy of 30- and 60-weeks of age were used in these studies. Determination of liver glucokinase enzyme activity, liver glycogen content and serum biochemistry parameters reflect the metabolic disorder in these mice. Echocardiography and surface electrocardiographs were used to evaluate cardiac function. Superoxide dismutase activity and malondialdehyde levels reflect oxidative stress in the myocardium. RNAseq, GO enrichment analysis and qPCR wereused to detect differences in the myocardial gene expression profiles of Gck w/- and Gck w/w mice. Results: Hyperglycemia and insulin resistance induced by decreased liver glucokinase expression and enzyme activity throughout the life of heterozygous Gck knockout mice do not yield body weight significant difference. However, prolonged PR interval and QRS duration, decreased left ventricular diameter and increased thickness of the posterior wall of the left ventricle were accompanied by increase of PAS and Masson positive substances in the myocardium of 60-week-old Gck knockout mice. RNAseq analysis showed that genes related tothe myosin heavy and light chains, insulin signaling pathway and oxidative phosphorylation were significantly differentially expressedbetween60-week-old Gck w/- and Gck w/w mice. Phosphorylation of AMPKβ1 and ACC in 60-week-old Gck knockout mice was decreased. Conclusions: Liver-specific Gck knock-out can induce myocardial fibrosis at an early stage and diabetic myocardial injury at alate stage. Through this process, the proportion of myosin heavy chain and light chain falls out of balance, the insulin signal pathway becomes down regulated and mitochondrial oxidative stress is up regulated, leading to myocardial disease.
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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 | 0.005 | 0.007 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.000 | 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".