Renal effects of glucagon‐like peptide‐1 receptor knockout in Akita‐diabetic mice
Bibliographic record
Abstract
Background Glucagon‐like peptide‐1 (GLP‐1) is a gut‐derived hormone that enhances glucose‐dependent insulin release and has anti‐oxidative and protective effects mediated through GLP‐1 receptor (GLP1R) in various tissues. Here, we determined whether the GLP1R has a pathophysiologic role in the diabetic kidney. Methods GLP1R‐KO mice (C57BL/6J) were backcrossed to DBA2 background for at least 4 generations and crossed with heterozygous Ins2 Akita mice, a genetic model of type 1 diabetes, to generate 4 experimental groups; i) WT (n=7), ii) GLP1R‐KO (n=14), iii) diabetic WT (n=6), and iv) diabetic GLP1R‐KO (n=10). Body weight, blood glucose, urine glucose and albumin to creatinine ratios, GFR (by plasma elimination kinetics of FITC‐sinistrin in conscious mice), and kidney weight were determined at 16 weeks of age. Results In non‐diabetic mice, no significant differences were observed between GLP1R‐KO and WT for bodyweight (26.1±1.0 vs 26±1.3 g), blood glucose (127±4 vs 112±5 mg/dl), urine glucose (2.5±0.3 vs 3.6±0.8 umol/mg), albuminuria (39±7 vs 37±19 μg/mg), and GFR (18±1 vs 22±2 μl/min/g), while kidney weight tended to be reduced in GLP1R‐KO (7.8±0.2 vs 8.5±0.3 mg/g; P=0.064). In GLP1R‐KO and WT mice, diabetes increased to similar levels: blood glucose (515±21 vs 501±32 mg/dl), urine glucose (3504±426 vs 5515±864 umol/mg), albuminuria (117±41 vs 102±22 ug/mg), food and fluid intake (not shown), and GFR (28±2 vs 33±3 ul/min/g), associated with a similar reduction in body weight (23.1±0.9 vs 23.7±0.6 g). While diabetes increased kidney weight in GLP1R‐KO and WT to similar absolute levels (11.8±0.8 vs 10.3±0.4 mg/g), the diabetes‐induced fractional increase was enhanced in GLP1R‐KO vs WT (increase of 51 vs 21%). Conclusion 1) On a predominant DBA2 genetic background, type 1 Akita diabetes increased blood glucose levels, GFR, kidney to body weight ratios, and albuminuria. 2) The effects of diabetes on blood glucose, GFR and albuminuria occurred independent of the GLP1R, whereas the absence of the GLP1R appeared to facilitate the diabetes‐induced increase in kidney to body weight ratios. Support or Funding Information National Institutes of Health (R01DK56248, P30DK079337) and AstraZeneca
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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) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".