Stevioside Potentiates Calcium Activity and Insulin Secretion in Human Pancreatic Islets Through Potentiation of TRPM5
Bibliographic record
Abstract
TRPM5 is a calcium‐activated monovalent cation channel that is expressed in human and murine islets. Ion channels of the TRP family are multimodal sensors and are activated by different stimuli such as voltage, temperature and ligands, including natural compounds. Previous work showed that mice lacking TRPM5 have increased postprandial blood glucose levels and an impaired insulin secretion. There are increased observations of TRPM5 mutations in patients suffering from diabetes or metabolic syndrome. Stevioside or stevia is a sweet‐tasting organic compound isolated from the plant Stevia rebaudiana, and is widely used as a low‐caloric sweetener. Despite the use of stevioside in consumer products, there is limited knowledge about its molecular interaction in the body. It was previously shown in mice that stevioside potentiates TRPM5, which leads to increased insulin secretion and ultimately better glycemic control in diabetic animal models. In this work, we translate these observations to freshly isolated human islets. We show that TRPM5 expression is limited to a subset of the insulin‐expressing beta‐cells in islets from non‐diabetic donors. In islets isolated from diabetic donors, we also see distinct TRPM5 positive cells that are insulin negative. There are substantial differences observed in the microanatomy of the islets and the functional synchronization of calcium signaling in beta cells between mouse and man. In perifusion studies, there is a potentiation of the glucose‐induced insulin secretion with the application of stevioside. These studies provide insight in the molecular mechanism of the action of stevioside in the human islets. Furthermore, we confirm the importance of TRPM5 in modulating the glucose‐stimulated insulin secretion in human islets. Modulating TRPM5 with stevioside constitutes a potential novel
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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".