Abstract 18777: Glucagon-like Peptide-1 Inhibits Thrombin-induced Human Platelet Aggregation
Bibliographic record
Abstract
Background: Studies of glycemic control in diabetics receiving glucagon-like peptide-1 (GLP-1)-targeted drugs have suggested reduced incidences of cardiovascular events over 6-12 months. Mechanisms underlying this surprisingly rapid effect are not known. Methods & Results: To investigate potential anti-thrombotic effects of GLP-1 and related analogs, we tested GLP-1(7-36)NH2, the most abundant endogenous GLP-1, and the commercially available GLP-1 analog exenatide in thrombin-induced platelet aggregation assays using freshly isolated gel-filtered human platelets (3x108/ml) in normoglycemic conditions (5.5mM glucose). Incubation with GLP-1 (10-10 to 10-6 M) or exenatide (5x10-10 to 10-8 M) for 15 min at 37°C delayed and reduced platelet aggregation as compared to PBS-treated controls. GLP-1 (10^-9M) resulted in a 60% decrease in aggregation 1 min after thrombin stimulation. To investigate whether this effect may be mediated by a GLP-1 receptor (R), whole cell lysates (40 µg) from gel-filtered human platelets and the human megakaryocyte (MGK) cell line MEG-01 were probed with a polyclonal anti- GLP-1R Ab (1:1250; Santa Cruz). Although Western blot showed bands (∼56 kD) consistent with the known GLP-1R in both platelets and MEG-01 cells, GAPDH-normalized expression levels of GLP-1R were ∼13 and ∼45 fold lower in these cells than in human pancreas. Given the limited specificity of Abs raised against GPCRs, RT-PCR was performed on RNA from MEG-01 cells with primers designed to yield full-length human GLP-1R cDNA. PCR products were cloned and sequenced, revealing inserts identical to GLP-1R. As this receptor is known to be adenylate cyclase-coupled, cAMP assays were also performed (EIA kit, Cayman Chemicals). MEG-01 cells incubated for 15 min with 10-7 M GLP-1 showed a ∼60% increase in intracellular cAMP, an inhibitor of platelet activation, as compared to untreated controls; while the cAMP response to prostacyclin PGI2 was much greater (positive control; 16 fold). Conclusion: Human platelets and MGK express low levels of GLP-1R. While GLP-1 induced only small increases in cAMP in MGK, both GLP-1 and exenatide inhibited thrombin-induced platelet aggregation. These data suggest that GLP-1-targeted drugs may possess anti-platelet effects.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.002 |
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".