Evidence map›Paper›PMID 16227617›Full record

ArticleMolecular and cellular biology2005

Muscle-specific deletion of the Glut4 glucose transporter alters multiple regulatory steps in glycogen metabolism.

Young-Bum Kim, Odile D Peroni, William G Aschenbach, Yasuhiko Minokoshi, Ko Kotani, Ariel Zisman, C Ronald Kahn, Laurie J Goodyear, Barbara B Kahn

Open access · greenAbstract read
In one paragraph

Article in Molecular and cellular biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
1.8field-weighted citation impact, top 16% 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

28 citing papers in PubMed, 56 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. AKT ISOFORMS-AS160-GLUT4: The defining axis of insulin resistance.Reviews in endocrine & metabolic disorders · 2021
    Review
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  19. Review
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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

9 authors at 3 institutions in 2 countries.

Young-Bum KimDivision of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, 99 Brookline Avenue, Boston, MA 02215, USA.
Odile D Peroni
William G Aschenbach
Yasuhiko Minokoshi
Ko Kotani
Ariel Zisman
C Ronald Kahn
Laurie J Goodyear
Barbara B Kahn
Hadassah Medical Center · ILHarvard University · USJoslin Diabetes Center · US

Funding

Transgenic CoreP30DK057521 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI KAHN, BARBARA B. · 2000 to 2019
$31.4M
Insulin Receptor Substrates and Insulin ActionR01DK033201 · NIDDK · JOSLIN DIABETES CENTER · PI KAHN, C RONALD · 1986 to 2016
$10.6M
Glucose Transporter Regulation in Obesity and DiabetesR37DK043051 · NIDDK · BETH ISRAEL DEACONESS MEDICAL CENTER · PI KAHN, BARBARA B. · 2006 to 2015
$5.0M
GLUCOSE TRANSPORTER REGULATION IN OBESITY AND DIABETESR01DK043051 · NIDDK · BETH ISRAEL DEACONESS MEDICAL CENTER · PI KAHN, BARBARA B. · 1992 to 2020
$4.4M
Regultion of Serine/Threonine Kinases in Skeletal MuscleR01DK068626 · NIDDK · JOSLIN DIABETES CENTER · PI GOODYEAR, LAURIE J · 2004 to 2012
$3.5M
Glucose Transporter Regulation in Obesity and DiabetesR56DK043051 · NIDDK · BETH ISRAEL DEACONESS MEDICAL CENTER · PI KAHN, BARBARA B. · 2022 to 2022
$173k
NIDDK NIH HHS DK 068626NIDDK NIH HHS DK 33201NIDDK NIH HHS DK 43051NIDDK NIH HHS DK 57521NIDDK NIH HHS P30 DK057521NIDDK NIH HHS R01 DK033201NIDDK NIH HHS R01 DK043051NIDDK NIH HHS R01 DK068626NIDDK NIH HHS R37 DK043051NIDDK NIH HHS R56 DK043051
6 · The paper itself

Abstract

Mice with muscle-specific knockout of the Glut4 glucose transporter (muscle-G4KO) are insulin resistant and mildly diabetic. Here we show that despite markedly reduced glucose transport in muscle, muscle glycogen content in the fasted state is increased. We sought to determine the mechanism(s). Basal glycogen synthase activity is increased by 34% and glycogen phosphorylase activity is decreased by 17% (P < 0.05) in muscle of muscle-G4KO mice. Contraction-induced glycogen breakdown is normal. The increased glycogen synthase activity occurs in spite of decreased signaling through the insulin receptor substrate 1 (IRS-1)-phosphoinositide (PI) 3-kinase-Akt pathway and increased glycogen synthase kinase 3beta (GSK3beta) activity in the basal state. Hexokinase II is increased, leading to an approximately twofold increase in glucose-6-phosphate levels. In addition, the levels of two scaffolding proteins that are glycogen-targeting subunits of protein phosphatase 1 (PP1), the muscle-specific regulatory subunit (RGL) and the protein targeting to glycogen (PTG), are strikingly increased by 3.2- to 4.2-fold in muscle of muscle-G4KO mice compared to wild-type mice. The catalytic activity of PP1, which dephosphorylates and activates glycogen synthase, is also increased. This dominates over the GSK3 effects, since glycogen synthase phosphorylation on the GSK3-regulated site is decreased. Thus, the markedly reduced glucose transport in muscle results in increased glycogen synthase activity due to increased hexokinase II, glucose-6-phosphate, and RGL and PTG levels and enhanced PP1 activity. This, combined with decreased glycogen phosphorylase activity, results in increased glycogen content in muscle in the fasted state when glucose transport is reduced.

Indexed as

AnimalsFastingFemaleGlucose-6-PhosphateGlucose Transporter Type 4GlycogenGlycogen PhosphorylaseGlycogen SynthaseGlycogen Synthase Kinase 3HexokinaseIntracellular Signaling Peptides and ProteinsIn Vitro TechniquesLiver GlycogenMaleMiceMice, KnockoutGlucose-6-PhosphateGlucose Transporter Type 4GlycogenGlycogen PhosphorylaseGlycogen SynthaseGlycogen Synthase Kinase 3HexokinaseIntracellular Signaling Peptides and ProteinsLiver GlycogenPhosphatidylinositol 3-KinasesPhosphoprotein PhosphatasesPpp1r3c protein, mouseProtein Phosphatase 1Proto-Oncogene Proteins c-aktSlc2a4 protein, mouse

Identifiers

PMID16227617
PMCPMC1265843
OpenAlexW2102214196

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.