1617-P: Small Intestinal Protein Sensing Mechanism in Feeding and Glucose Regulation
Bibliographic record
Abstract
Protein activates small intestinal calcium sensing receptor (CaSR) and/or peptide transporter 1 (PepT1) to increase GLP-1, but the role in glucose and feeding regulation remains elusive. We performed intravenous glucose tolerance test and refeeding studies and infused 8% (w/v) casein hydrolysate into the upper small intestine (USI) or ileum of male rats. We found that USI casein vs. saline infusion increased glucose tolerance in chow (p<0.01) and HF-fed rats (p<0.05) and suppressed feeding in chow (p<0.01) but not HF rats. We inhibited CaSR via injecting lentivirus expressing shRNA of CaSR into the USI (reduced expression by ~40%) and CaSR knockdown negated casein to increase glucose tolerance but not to lower feeding (p<0.01). Instead, viral-mediated PepT1 knockdown by ~50% negated casein to lower feeding as similar to previously reported for glucose control. Thus, CaSR and PepT1 are required for casein in the USI to increase glucose tolerance, while PepT1 but not CaSR mediates casein to lower feeding, in chow rats. The differential role of PepT1 vs CaSR may explain why HF disrupts casein to regulate feeding but not glucose tolerance as HF inhibited PepT1 expression (p<0.05) but increased CaSR expression (p<0.05) in the USI. Ileal casein vs saline infusion increased glucose tolerance (p<0.01) and lowered feeding (p<0.01). Ileal CaSR inhibition negated casein vs saline to increase glucose tolerance and lower feeding, whereas ileal PepT1 inhibition failed to do so, indicating that ileal casein regulates glucose tolerance and food intake via PepT1-independent but CaSR-dependent pathways in chow rats. HF feeding inhibited ileal CaSR expression by ~60% (p<0.05) in association with a disruption in ileal casein action on feeding but surprisingly not on glucose control (p<0.01), suggesting that ileal casein could even regulate glucose tolerance independent of CaSR. In sum, we discover differential role of CaSR vs. PepT1 in the USI and ileum that alter feeding and glucose regulatory abilities of protein sensing. Disclosure D.Barros: None. R.J.W.Li: None. Y.Lim: None. S.Zhang: None. R.Kuah: None. A.Gao: None. T.K.Lam: None. Funding Canadian Institutes of Health Research (PJT183901)
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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".