Central Resistin Induces Hepatic Insulin Resistance via Neuropeptide Y
Bibliographic record
Abstract
Sensing of peripheral hormones and nutrients by the hypothalamus plays an important role in maintaining peripheral glucose homeostasis. The hormone resistin impairs the response to insulin in liver and other peripheral tissues. Here we demonstrate that in normal mice resistin delivered in the lateral cerebral ventricle increased endogenous glucose production during hyperinsulinemic-euglycemic clamp, consistent with induction of hepatic insulin resistance. In agreement, central resistin inhibited Akt phosphorylation and increased the expression of glucose-6-phosphatase, the enzyme regulating glucose output in the liver. Central resistin induced expression of proinflammatory cytokines as well as suppressor of cytokine signaling-3, a negative regulator of insulin action in liver. Central infusion of resistin was associated with neuronal activation in the arcuate, paraventricular and dorsomedial nuclei, and increased neuropeptide Y (NPY) expression in the hypothalamus. The effects of central resistin on glucose production as well as hepatic expression of proinflammatory cytokines were abrogated in mice lacking NPY. Pretreatment of wild-type mice with antagonists of the NPY Y1 receptor, but not the Y5 receptor, also prevented the effects of central resistin. Together, these results suggest that resistin action on NPY neurons is an important regulator of hepatic insulin sensitivity.
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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 | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 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".