Hydrogen Sulfide Impairs Glucose Utilization and Increases Gluconeogenesis in Hepatocytes
Bibliographic record
Abstract
Mounting evidence has established hydrogen sulfide (H(2)S) as an important gasotransmitter with multifaceted physiological functions. The aim of the present study was to investigate the role of H(2)S on glucose utilization, glycogen synthesis, as well as gluconeogenesis in both HepG(2) cells and primary mouse hepatocytes. Incubation with NaHS (a H(2)S donor) impaired glucose uptake and glycogen storage in HepG(2) cells via decreasing glucokinase activity. Adenovirus-mediated cystathionine γ-lyase (CSE) overexpression increased endogenous H(2)S production and lowered glycogen content in HepG(2) cells. Glycogen content was significantly higher in liver tissues from CSE knockout (KO) mice compared to that from wild type (WT) mice in fed condition. Glucose consumption was less in primarily cultured hepatocytes isolated from WT mice than those from CSE KO mice, but more glucose was produced by hepatocytes via gluconeogenesis and glycogenolysis pathways in WT mice than in CSE KO mice. NaHS treatment reduced the phosphorylation of AMP-activated protein kinase, whereas stimulation of AMP-activated protein kinase by 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside reversed H(2)S-impaired glucose uptake. H(2)S-increased glucose production was likely through increased phosphoenolpyruvate carboxykinase activity. In addition, insulin at the physiological range inhibited CSE expression, and H(2)S decreased insulin-stimulated phosphorylation of Akt in HepG(2) cells. CSE expression was increased, however, in insulin-resistant state induced by exposing cells to high levels of insulin (500 nm) and glucose (33 mm) for 24 h. Taken together, these data suggest that the interaction of H(2)S and insulin in liver plays a pivotal role in regulating insulin sensitivity and glucose metabolism.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".