Liver-derived fibroblast growth factor 21 mediates effects of glucagon-like peptide-1 in attenuating hepatic glucose output
Bibliographic record
Abstract
BACKGROUND: Glucagon-like peptide-1 (GLP-1) and its based agents improve glycemic control. Although their attenuating effect on hepatic glucose output has drawn our attention for decades, the potential mechanisms remain unclear. METHODS: ) were treated with a GLP-1 analog exenatide or liraglutide. The expression and secretion of fibroblast growth factor 21 (FGF21) in the livers of diabetic mice, primary mouse and human hepatocytes, and the human hepatic cell line HepG2 treated with or without GLP-1 analog were measured. Blockage of FGF21 with neutralizing antibody or siRNA, or hepatocytes isolated from Fgf21 knockout mice were used, and the expression and activity of key enzymes in gluconeogenesis were analyzed. Serum FGF21 level was evaluated in patients with type 2 diabetes (T2D) receiving exenatide treatment. FINDINGS: Utilizing the cytokine array, we identified that FGF21 secretion was upregulated by exenatide (exendin-4). Similarly, FGF21 production in hepatocytes was stimulated by exenatide or liraglutide. FGF21 blockage attenuated the inhibitory effects of the GLP-1 analogs on hepatic glucose output. Similar results were also observed in primary hepatocytes from Fgf21 knockout mice. Furthermore, exenatide treatment increased serum FGF21 level in patients with T2D, particularly in those with better glucose control. INTERPRETATION: We identify that function of GLP-1 in inhibiting hepatic glucose output is mediated via the liver hormone FGF21. Thus, we provide a new extra-pancreatic mechanism by which GLP-1 regulates glucose homeostasis. FUND: National Key Research and Development Program of China, the National Natural Science Foundation of China, the Natural Science Foundation of Beijing and Peking University Medicine Seed Fund for Interdisciplinary 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) | 0.000 | 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) | 0.002 | 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 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".