OATP1B3 Is Expressed in Pancreatic β-Islet Cells and Enhances the Insulinotropic Effect of the Sulfonylurea Derivative Glibenclamide
Bibliographic record
Abstract
Organic anion transporting polypeptide OATP1B3 is a membrane-bound drug transporter that facilitates cellular entry of a variety of substrates. Most of the previous studies focused on its hepatic expression and function in hepatic drug elimination. In this study, we report expression of OATP1B3 in human pancreatic tissue, with the abundance of the transporter localized in the islets of Langerhans. Transport studies using OATP1B3-overexpressing MDCKII cells revealed significant inhibition of the cellular uptake of the known substrate cholecystokinin-8 in the presence of the insulinotropic antidiabetes compounds tolbutamide, glibenclamide, glimepiride, and nateglinide and identified glibenclamide as a novel substrate of OATP1B3. Sulfonylurea derivatives exert their insulinotropic effect by binding to the SUR1 subunit of the KATP channels inducing insulin secretion in β-cells. Here, we show that transient overexpression of human OATP1B3 in a murine β-cell line (MIN6)-which exhibits glucose and glibenclamide-sensitive insulin secretion-significantly enhances the insulinotropic effect of glibenclamide without affecting glucose-stimulated insulin secretion. Taken together, our data provide evidence that the drug transporter OATP1B3 functions as a determinant of the insulinotropic effect of glibenclamide on the tissue level. Changes in transport activity based on drug-drug interactions or genetic variability may therefore influence glibenclamide efficacy.
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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".