Pioglitazone Acutely Reduces Insulin Secretion and Causes Metabolic Deceleration of the Pancreatic β-Cell at Submaximal Glucose Concentrations
Bibliographic record
Abstract
Thiazolidinediones (TZDs) have beneficial effects on glucose homeostasis via enhancement of insulin sensitivity and preservation of beta-cell function. How TZDs preserve beta-cells is uncertain, but it might involve direct effects via both peroxisome proliferator-activated receptor-gamma-dependent and -independent pathways. To gain insight into the independent pathway(s), we assessed the effects of short-term (<or=90 min) exposure to pioglitazone (Pio) (10 to 50 microM) on glucose-induced insulin secretion (GIIS), AMP-activated protein kinase (AMPK) activation, and beta-cell metabolism in INS 832/13 beta-cells and rat islets. Pio caused a right shift in the dose-dependence of GIIS, such that insulin release was reduced at intermediate glucose but unaffected at either basal or maximal glucose concentrations. This was associated in INS 832/13 cells with alterations in energy metabolism, characterized by reduced glucose oxidation, mitochondrial membrane polarization, and ATP levels. Pio caused AMPK phosphorylation and its action on GIIS was reversed by the AMPK inhibitor compound C. Pio also reduced palmitate esterification into complex lipids and inhibited lipolysis. As for insulin secretion, the alterations in beta-cell metabolic processes were mostly alleviated at elevated glucose. Similarly, the antidiabetic agents and AMPK activators metformin and berberine caused a right shift in the dose dependence of GIIS. In conclusion, Pio acutely reduces glucose oxidation, energy metabolism, and glycerolipid/fatty acid cycling of the beta-cell at intermediate glucose concentrations. We suggest that AMPK activation and the metabolic deceleration of the beta-cell caused by Pio contribute to its known effects to reduce hyperinsulinemia and preserve beta-cell function and act as an antidiabetic agent.
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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".