1197-P: Effect of Somatostatin Receptor 2 Antagonist (SSTR2a) on Glycemia and Glucagon Levels in a Rat Model of Type 2 Diabetes (T2D)
Bibliographic record
Abstract
Background: Defective glucagon counterregulation to hypoglycemia in T1D involves elevated somatostatin signalling on the α cell. In rats, SSTR2a treatment (ZT-01 <1 mg/kg) restores normal response in hypoglycemica and higher doses (≥3 mg/kg) transiently increase glucagon in euglycemia. In T2D, glucagon counterregulation to hypoglycemia may also be blunted, but SSTR2a has not been evaluated. We test the effect of high dose (3 mg/kg) ZT-01 in hyperglycemia in T2D and in euglycemia.Methods: High fat fed, low dose streptozotocin (T2D) and healthy rats were treated with subcutaneous ZT-01 or vehicle (N=7-8/group). Glycemia, glucagon and C-peptide were measured for 4 h post-dose.Results: SSTR2a treatment promoted a significant rise in basal glucagon in both T2D and control rats, up to 3 hours post-dose. Basal C-peptide was lower in T2D versus healthy rats (1.9 vs. 2.5 ng/ml) increasing in both groups 30 min after SSTR2a dosing (2.7 vs. 4.1 ng/mL). Both diabetes (p=0.03) and treatment (p=0.01) were significant effects (2-way ANOVA). Post-dose glucose was elevated from baseline in T2D but not in healthy rats.Conclusion: High dose SSTR2a transiently increased glucagon. C-peptide was increased to a lesser extent in T2D. Consequently, glucose levels were affected in T2D but not healthy rats. Insulin production and sensitivity in T2D may play an important role in responses to SSTR2a in this model.View largeDownload slideView largeDownload slide DisclosureN. C. D'souza: None. E. G. Hoffman: None. S. C. Atherley: None. S. Champsi: None. M. Popkov: None. R. Liggins: Employee; Self; Zucara Therapeutics Inc. M. Riddell: Advisory Panel; Self; Zealand Pharma A/S, Consultant; Self; Lilly Diabetes, Research Support; Self; Dexcom, Inc., Insulet Corporation, Speaker's Bureau; Self; Novo Nordisk Inc., Sanofi, Stock/Shareholder; Self; Zucara Therapeutics Inc.FundingGlycoNet
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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 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".