Evidence map›Paper›PMID 25875045›Full record

ArticleMolecular endocrinology (Baltimore, Md.)2015

Involvement of mTOR in Type 2 CRF Receptor Inhibition of Insulin Signaling in Muscle Cells.

Hongxia Chao, Haochen Li, Rebecca Grande, Vitor Lira, Zhen Yan, Thurl E Harris, Chien Li

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular endocrinology (Baltimore, Md.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.4field-weighted citation impact, top 35% 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

4 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. 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

7 authors at 1 institution in 1 country.

Hongxia ChaoDepartments of Pharmacology (H.C., H.L., R.G., Z.Y., T.H., C.L.), Medicine (V.L., Z.Y.), and Molecular Physiology and Biophysics (Z.Y.), and Center for Skeletal Muscle Research at Robert M. Berne Cardiovascular Research Center (Z.Y.), University of Virginia Health System, Charlottesville, Virginia 22908.
Haochen LiDepartments of Pharmacology (H.C., H.L., R.G., Z.Y., T.H., C.L.), Medicine (V.L., Z.Y.), and Molecular Physiology and Biophysics (Z.Y.), and Center for Skeletal Muscle Research at Robert M. Berne Cardiovascular Research Center (Z.Y.), University of Virginia Health System, Charlottesville, Virginia 22908.
Rebecca GrandeDepartments of Pharmacology (H.C., H.L., R.G., Z.Y., T.H., C.L.), Medicine (V.L., Z.Y.), and Molecular Physiology and Biophysics (Z.Y.), and Center for Skeletal Muscle Research at Robert M. Berne Cardiovascular Research Center (Z.Y.), University of Virginia Health System, Charlottesville, Virginia 22908.
Vitor LiraDepartments of Pharmacology (H.C., H.L., R.G., Z.Y., T.H., C.L.), Medicine (V.L., Z.Y.), and Molecular Physiology and Biophysics (Z.Y.), and Center for Skeletal Muscle Research at Robert M. Berne Cardiovascular Research Center (Z.Y.), University of Virginia Health System, Charlottesville, Virginia 22908.
Zhen YanDepartments of Pharmacology (H.C., H.L., R.G., Z.Y., T.H., C.L.), Medicine (V.L., Z.Y.), and Molecular Physiology and Biophysics (Z.Y.), and Center for Skeletal Muscle Research at Robert M. Berne Cardiovascular Research Center (Z.Y.), University of Virginia Health System, Charlottesville, Virginia 22908.
Thurl E HarrisDepartments of Pharmacology (H.C., H.L., R.G., Z.Y., T.H., C.L.), Medicine (V.L., Z.Y.), and Molecular Physiology and Biophysics (Z.Y.), and Center for Skeletal Muscle Research at Robert M. Berne Cardiovascular Research Center (Z.Y.), University of Virginia Health System, Charlottesville, Virginia 22908.
Chien LiDepartments of Pharmacology (H.C., H.L., R.G., Z.Y., T.H., C.L.), Medicine (V.L., Z.Y.), and Molecular Physiology and Biophysics (Z.Y.), and Center for Skeletal Muscle Research at Robert M. Berne Cardiovascular Research Center (Z.Y.), University of Virginia Health System, Charlottesville, Virginia 22908.
University of Virginia Health System · US

Funding

p38 MAPK a regulator of muscle contraction and functionR01AR050429 · NIAMS · VIRGINIA POLYTECHNIC INST AND ST UNIV · PI YAN, ZHEN · 2005 to 2022
$5.3M
Role of Oxidized neutral lipids in adipocyte functionR01DK101946 · NIDDK · UNIVERSITY OF VIRGINIA · PI HARRIS, THURL E. · 2014 to 2018
$1.7M
Central Neural Function of Urocortin 3 in Regulating Energy BalanceR01DK078049 · NIDDK · UNIVERSITY OF VIRGINIA · PI LI, CHIEN · 2009 to 2013
$1.6M
NIAMS NIH HHS R01 AR050429NIDDK NIH HHS R01 DK078049NIDDK NIH HHS R01 DK101946
6 · The paper itself

Abstract

Type 2 corticotropin-releasing factor receptor (CRFR2) is expressed in skeletal muscle and stimulation of the receptor has been shown to inhibit the effect of insulin on glucose uptake in muscle cells. Currently, little is known about the mechanisms underlying this process. In this study, we first showed that both in vivo and in vitro CRFR2 expression in muscle was closely correlated with insulin sensitivity, with elevated receptor levels observed in insulin resistant muscle cells. Stimulation of CRFR2 by urocortin 2 (Ucn 2), a CRFR2-selective ligand, in C2C12 myotubes greatly attenuated insulin-induced glucose uptake. The inhibitory effect of CRFR2 signaling required cAMP production and is involved the mammalian target of rapamycine pathway, as rapamycin reversed the inhibitory effect of CRFR2 stimulation on insulin-induced glucose uptake. Moreover, stimulation of CRFR2 failed to inhibit glucose uptake in muscle cells induced by platelet-derived growth factor, which, similar to insulin, signals through Akt-mediated pathway but is independently of insulin receptor substrate (IRS) proteins to promote glucose uptake. This result argues that CRFR2 signaling modulates insulin's action likely at the levels of IRS. Consistent with this notion, Ucn 2 reduced insulin-induced tyrosine phosphorylation of IRS-1, and treatment with rapamycin reversed the inhibitory effect of Ucn 2 on IRS-1 and Akt phosphorylation. In conclusion, the inhibitory effect of CRFR2 signaling on insulin action is mediated by cAMP in a mammalian target of rapamycine-dependent manner, and IRS-1 is a key nodal point where CRFR2 signaling modulates insulin-stimulated glucose uptake in muscle cells.

Indexed as

Signal TransductionAdenylyl CyclasesAnimalsCell DifferentiationCell LineDeoxyglucoseDisease Models, AnimalGene Knockdown TechniquesInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceMaleMice, ObeseModels, BiologicalMuscle CellsMuscle Fibers, SkeletalAdenylyl CyclasesCRF receptor type 2DeoxyglucoseInsulinInsulin Receptor Substrate ProteinsPhosphotyrosinePlatelet-Derived Growth FactorProto-Oncogene Proteins c-aktReceptors, Corticotropin-Releasing HormoneSirolimusTOR Serine-Threonine KinasesUrocortins

Identifiers

PMID25875045
PMCPMC4447643
OpenAlexW1970987692

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.