Evidence map›Paper›PMID 21398515›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2011

Mechanistic modeling of the effects of glucocorticoids and circadian rhythms on adipokine expression.

Siddharth Sukumaran, William J Jusko, Debra C DuBois, Richard R Almon

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of pharmacology and experimental therapeutics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.1field-weighted citation impact, top 28% 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

19 citing papers in PubMed, 31 citations in OpenAlex.

  1. Adiponectin and Glucocorticoids Modulate Risk for Preterm Birth: The Healthy Start Study.The Journal of clinical endocrinology and metabolism · 2025
    Article
  2. Review
  3. Review
  4. Review
  5. Review
  6. Review
  7. Article
  8. Article
  9. Indirect pharmacodynamic models for responses with circadian removal.Journal of pharmacokinetics and pharmacodynamics · 2019
    Article
  10. Article
  11. Delayed logistic indirect response models: realization of oscillating behavior.Journal of pharmacokinetics and pharmacodynamics · 2018
    Article
  12. Article
  13. Article
  14. Article
  15. Systems Chronotherapeutics.Pharmacological reviews · 2017
    Review
  16. Article
  17. Article
  18. Article
  19. Review
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

4 authors at 1 institution in 1 country.

Siddharth SukumaranDepartment of Biological Sciences, State University of New York, Buffalo, NY 14260, USA.
William J Jusko
Debra C DuBois
Richard R Almon
University at Buffalo, State University of New York · US

Funding

Corticosteroid Pharmacokinetics and PharmacodynamicsR37GM024211 · NIGMS · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI JUSKO, WILLIAM J. · 2005 to 2014
$6.4M
CORTICOSTEROID PHARMACOKINETICS/DYNAMICSR01GM024211 · NIGMS · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI JUSKO, WILLIAM J. · 1985 to 2018
$4.7M
NIGMS NIH HHS GM24211NIGMS NIH HHS R01 GM024211NIGMS NIH HHS R37 GM024211
6 · The paper itself

Abstract

A mechanism-based model was developed to describe the effects of methylprednisolone (MPL), circadian rhythms, and the glucose/free fatty acid (FFA)/insulin system on leptin and adiponectin expression in white adipose tissue in rats. Fifty-four normal Wistar rats received 50 mg/kg MPL intramuscularly and were sacrificed at various times. An additional set of 54 normal Wistar rats were sacrificed at 18 time points across the 24-h light/dark cycle and served as controls. Measurements included plasma MPL, glucocorticoid receptor (GR) mRNA, leptin mRNA, adiponectin mRNA, plasma leptin, adiponectin, glucose, FFA, and insulin. MPL pharmacokinetics was described by a two-compartment model with two absorption components. All measured plasma markers and mRNA expression exhibited circadian patterns except for adiponectin and were described by Fourier harmonic functions. MPL caused significant down-regulation in GR mRNA with the nadir occurring at 5 h. MPL disrupted the circadian patterns in plasma glucose and FFA by stimulating their production. Plasma glucose and FFA subsequently caused an increase in plasma insulin. Furthermore, MPL disrupted the circadian patterns in leptin mRNA expression by stimulating its production. This rise was closely followed by an increase in plasma leptin. Both leptin mRNA and plasma leptin peaked at 12 h after MPL and eventually returned back to their circadian baselines. MPL and insulin had opposing effects on adiponectin mRNA expression and plasma adiponectin, which resulted in biphasic pharmacodynamic profiles. This small systems model quantitatively describes, integrates, and provides additional insights into various factors controlling adipokine gene expression.

Indexed as

Circadian RhythmAdiponectinAdipose Tissue, WhiteAnimalsBlood GlucoseDown-RegulationFatty Acids, NonesterifiedGlucocorticoidsInsulinLeptinMaleMethylprednisoloneModels, BiologicalRatsRats, WistarReceptors, GlucocorticoidAdiponectinBlood GlucoseFatty Acids, NonesterifiedGlucocorticoidsInsulinLeptinMethylprednisoloneReceptors, GlucocorticoidRNA, Messenger

Identifiers

PMID21398515
PMCPMC3101012
OpenAlexW2132921286

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.