Evidence mapPaperPMID 25890210Full record

ArticleJournal of translational medicine2015

Effects of the glucagon-like peptide-1 receptor agonist liraglutide in juvenile transgenic pigs modeling a pre-diabetic condition.

Elisabeth Streckel, Christina Braun-Reichhart, Nadja Herbach, Maik Dahlhoff, Barbara Kessler, Andreas Blutke, Andrea Bähr, Nicole Übel, Matthias Eddicks, Mathias Ritzmann and 6 more

Open access · goldFull text read
In one paragraph

Article in Journal of translational medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
4.1field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 26 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Mild maternal hyperglycemia inDisease models & mechanisms · 2019
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Animal models of obesity and diabetes mellitus.Nature reviews. Endocrinology · 2018
    Review
  11. Review
  12. Review
  13. MiRNA-323-5p Promotes U373 Cell Apoptosis by Reducing IGF-1R.Medical science monitor : international medical journal of experimental and clinical research · 2015
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 2 institutions in 1 country.

Elisabeth StreckelChair for Molecular Animal Breeding and Biotechnology, Gene Center, LMU Munich, Munich, Germany. e.streckel@gen.vetmed.uni-muenchen.de.
Christina Braun-ReichhartChair for Molecular Animal Breeding and Biotechnology, Gene Center, LMU Munich, Munich, Germany. c.braun@gen.vetmed.uni-muenchen.de.
Nadja HerbachInstitute of Veterinary Pathology, Center for Clinical Veterinary Medicine, LMU Munich, Munich, Germany. herbach@patho.vetmed.uni-muenchen.de.
Maik DahlhoffChair for Molecular Animal Breeding and Biotechnology, Gene Center, LMU Munich, Munich, Germany. dahlhoff@lmb.uni-muenchen.de.
Barbara KesslerChair for Molecular Animal Breeding and Biotechnology, Gene Center, LMU Munich, Munich, Germany. b.kessler@gen.vetmed.uni-muenchen.de.
Andreas BlutkeInstitute of Veterinary Pathology, Center for Clinical Veterinary Medicine, LMU Munich, Munich, Germany. blutke@patho.vetmed.uni-muenchen.de.
Andrea BährChair for Molecular Animal Breeding and Biotechnology, Gene Center, LMU Munich, Munich, Germany. a.baehr@gen.vetmed.uni-muenchen.de.
Nicole ÜbelClinic for Swine, Center for Clinical Veterinary Medicine, LMU Munich, Munich, Germany. N.Uebel@med.vetmed.uni-muenchen.de.
Matthias EddicksClinic for Swine, Center for Clinical Veterinary Medicine, LMU Munich, Munich, Germany. m.eddicks@lmu.de.
Mathias RitzmannClinic for Swine, Center for Clinical Veterinary Medicine, LMU Munich, Munich, Germany. Ritzmann@med.vetmed.uni-muenchen.de.
Stefan KrebsLaboratory for Functional Genome Analysis (LAFUGA), Gene Center, LMU Munich, Munich, Germany. krebs-st@lmb.uni-muenchen.de.
Burkhard GökeDepartment of Internal Medicine II, Clinical Center of the LMU Munich, Campus Großhadern, Munich, Germany. burkhard.goeke@med.uni-muenchen.de.
Helmut BlumLaboratory for Functional Genome Analysis (LAFUGA), Gene Center, LMU Munich, Munich, Germany. blum@genzentrum.lmu.de.
Rüdiger WankeInstitute of Veterinary Pathology, Center for Clinical Veterinary Medicine, LMU Munich, Munich, Germany. wanke@patho.vetmed.uni-muenchen.de.
Eckhard WolfChair for Molecular Animal Breeding and Biotechnology, Gene Center, LMU Munich, Munich, Germany. ewolf@lmb.uni-muenchen.de.
Simone RennerChair for Molecular Animal Breeding and Biotechnology, Gene Center, LMU Munich, Munich, Germany. s.renner@gen.vetmed.uni-muenchen.de.
Ludwig-Maximilians-Universität München · DELMU Klinikum · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe glucagon-like peptide-1 receptor (GLP1R) agonist liraglutide improves glycemic control and reduces body weight of adult type 2 diabetic patients. However, efficacy and safety of liraglutide in adolescents has not been systematically investigated. Furthermore, possible pro-proliferative effects of GLP1R agonists on the endocrine and exocrine pancreas need to be further evaluated. We studied effects of liraglutide in adolescent pigs expressing a dominant-negative glucose-dependent insulinotropic polypeptide receptor (GIPR(dn)) in the beta-cells, leading to a pre-diabetic condition including disturbed glucose tolerance, reduced insulin secretion and progressive reduction of functional beta-cell mass.

methodsTwo-month-old GIPR(dn) transgenic pigs were treated daily with liraglutide (0.6-1.2 mg per day) or placebo for 90 days. Glucose homeostasis was evaluated prior to and at the end of the treatment period by performing mixed meal and intravenous glucose tolerance tests (MMGTT and IVGTT). Finally animals were subjected to necropsy and quantitative-stereological analyses were performed for evaluation of alpha- and beta-cell mass, beta-cell proliferation as well as acinus-cell proliferation.

resultsMMGTT at the end of the study revealed 23% smaller area under the curve (AUC) for glucose, a 36% smaller AUC insulin, and improved insulin sensitivity, while IVGTT showed a 15% smaller AUC glucose but unchanged AUC insulin in liraglutide- vs. placebo-treated animals. Liraglutide led to marked reductions in body weight gain (-31%) and food intake (-30%) compared to placebo treatment, associated with reduced phosphorylation of insulin receptor beta (INSRB)/insulin-like growth factor-1 receptor beta (IGF1RB) and protein kinase B (AKT) in skeletal muscle. Absolute alpha- and beta-cell mass was reduced in liraglutide-treated animals, but alpha- and beta-cell mass-to-body weight ratios were unchanged. Liraglutide neither stimulated beta-cell proliferation in the endocrine pancreas nor acinus-cell proliferation in the exocrine pancreas, excluding both beneficial and detrimental effects on the pig pancreas.

conclusionsAlthough plasma liraglutide levels of adolescent transgenic pigs treated in our study were higher compared to human trials, pro-proliferative effects on the endocrine or exocrine pancreas or other liraglutide-related side-effects were not observed.

Indexed as

Glucagon-Like Peptide-1 Receptor AgonistsAcinar CellsAnimalsAnimals, Genetically ModifiedBlood GlucoseCell ProliferationCell SizeDisease Models, AnimalFeeding BehaviorGastric EmptyingGlucagon-Like Peptide-1 ReceptorGlucose Tolerance TestInsulinInsulin SecretionLiraglutideMuscle, SkeletalBlood GlucoseGlucagon-Like Peptide-1 ReceptorGlucagon-Like Peptide-1 Receptor AgonistsInsulinLiraglutideTOR Serine-Threonine Kinases

Identifiers

PMID25890210
PMCPMC4362632
OpenAlexW2049073771

What Socratic holds

Textfull text, public
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.