2036-P: Gut Microbes Regulate Insulin Clearance in Mice
Bibliographic record
Abstract
Obesity and insulin resistance are associated with hyperinsulinemia, which is caused by increased insulin secretion and/or reduced insulin clearance. Impaired insulin clearance may be caused by ectopic lipid deposition in liver and skeletal muscle, the key sites of insulin clearance and degradation. Insulin is the key hormone regulating blood glucose. The composition of the intestinal microbiota can regulate aspects of diet-induced obesity and glucose metabolism. Here we found that the microbiota also regulates insulin clearance during prolonged diet-induced obesity. Male C57Bl/6J mice fed 45% high fat diet (HFD) for a prolonged period had impaired insulin clearance relative to chow fed mice as measured by insulin/C-peptide ratio during an oral glucose tolerance test. High fat fed mice also showed impaired insulin clearance measured after injection of insulin - mice fed chow or 45% HFD had plasma insulin concentration measured at 0, 5, 30, and 60 minutes following injection of human insulin and area under the curve calculated. Treatment of 45% HFD-fed mice with an antibiotic cocktail of Neomycin/Ampicillin for 2 weeks improved insulin clearance after insulin injection. Next, we colonized previously germ-free mice with the microbiota from chow or 45% HFD-fed “donor” mice for 6 weeks. The previously germ-free “recipient” mice colonized with feces-resident microbes from chow or HFD fed donors did not differ in insulin clearance when recipient mice were fed a chow diet. However, when colonized recipient mice were switched from chow to 45% HFD for 2 weeks the recipient mice colonized with microbes from 45% HFD fed donors showed impaired insulin clearance relative to recipient mice colonized with microbes from chow fed donors. Our results demonstrate that diet-induced changes in fecal microbes are an independent factor regulating insulin clearance. Diet-induced changes in the gut microbiota and consequent impaired insulin clearance may participate in hyperinsulinemia leading to exacerbated insulin resistance and obesity. Disclosure K.P. Foley: None. S. Zlitni: None. B.M. Duggan: None. B.D. Henriksbo: None. N.G. Barra: None. J.F. Cavallari: None. F. Forato Anhê: None. T. Lau: None. Y. Chen: None. J.D. Schertzer: None. Funding Canadian Institutes of Health Research
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.003 | 0.006 |
| Insufficient payload (model declined to judge) | 0.026 | 0.014 |
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 source (direct Gemma or distilled Codex), 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".