Evidence map›Paper›PMID 22846604›Full record

ArticleBiochimica et biophysica acta2012

Preventing the calorie restriction-induced increase in insulin-stimulated Akt2 phosphorylation eliminates calorie restriction's effect on glucose uptake in skeletal muscle.

Naveen Sharma, Edward B Arias, Donel A Sequea, Gregory D Cartee

Open access · greenAbstract read
In one paragraph

Article in Biochimica et biophysica acta, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.5field-weighted citation impact, top 19% 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

21 citing papers in PubMed, 27 citations in OpenAlex.

  1. Trial
  2. Sex-specific phosphoproteome responses to calorie restriction and insulin in skeletal muscle from older rats.The journals of gerontology. Series A, Biological sciences and medical sciences · 2025
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  10. Inhibition of Akt2 phosphorylation abolishes the calorie restriction-induced improvement in insulin-stimulated glucose uptake by rat soleus muscle.Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme · 2016
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  12. Calorie restriction leads to greater Akt2 activity and glucose uptake by insulin-stimulated skeletal muscle from old rats.American journal of physiology. Regulatory, integrative and comparative physiology · 2016
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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

4 authors at 1 institution in 1 country.

Naveen SharmaMuscle Biology Laboratory, School of Kinesiology, University of Michigan, Ann Arbor, MI 48109-2214, USA. naveens@umich.edu
Edward B Arias
Donel A Sequea
Gregory D Cartee
University of Michigan · US

Funding

Research DevelopmentP30AG013283 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MILLER, RICHARD A · 1995 to 2014
$12.3M
Aging, Calorie Restriction, Exercise and Insulin SensitivityR01AG010026 · NIA · UNIVERSITY OF WISCONSIN MADISON · PI CARTEE, GREGORY D. · 1998 to 2023
$6.8M
AGE EFFECTS ON EXERCISE-STIMULATION OF GLUCOSE TRANSPORTR29AG010026 · NIA · UNIVERSITY OF WISCONSIN MADISON · PI CARTEE, GREGORY D. · 1992 to 1996
–
NIA NIH HHS AG-010026NIA NIH HHS AG-013283NIA NIH HHS P30 AG013283NIA NIH HHS R01 AG010026
6 · The paper itself

Abstract

Calorie restriction (CR; ~60% of ad libitum, AL, consumption) improves insulin-stimulated glucose uptake in skeletal muscle. The precise cellular mechanism for this healthful outcome is unknown, but it is accompanied by enhanced insulin-stimulated activation of Akt. Previous research using Akt2-null mice demonstrated that Akt2 is essential for the full CR-effect on insulin-stimulated glucose uptake by muscle. However, because Akt2-null mice were completely deficient in Akt2 in every cell throughout life, it would be valuable to assess the efficacy of transient, muscle-specific Akt inhibition for attenuation of CR-effects on glucose uptake. Accordingly, we used a selective Akt inhibitor (MK-2206) to eliminate the CR-induced elevation in insulin-stimulated Akt2 phosphorylation and determined the effects on Akt substrates and glucose uptake. We incubated isolated epitrochlearis muscles from 9-month-old AL and CR (~60-65% of AL intake for 6months) rats with or without MK-2206 and measured insulin-stimulated (1.2nM) glucose uptake and phosphorylation of the insulin receptor (Tyr1162/1163), pan-Akt (Thr308 and Ser473), Akt2 (Thr308 and Ser473), AS160/TBC1D4 (Thr642), and Filamin C (Ser2213). Incubation of isolated skeletal muscles with a dose of a selective Akt inhibitor that eliminated the CR-induced increases in Akt2 phosphorylation prevented CR's effects on insulin-stimulated glucose uptake, pAS160(Thr642) and pFilamin C(Ser2213) without altering pIR(Tyr1162/1163). These data provide compelling new evidence linking the CR-induced increase in insulin-stimulated Akt2 phosphorylation to CR's effects on insulin-mediated phosphorylation of Akt substrates and glucose uptake in skeletal muscle.

Indexed as

Caloric RestrictionProto-Oncogene Proteins c-aktAnimalsContractile ProteinsFilaminsGlucoseHeterocyclic Compounds, 3-RingInsulinMicrofilament ProteinsMuscle, SkeletalPhosphorylationRatsReceptor, InsulinAkt2 protein, ratContractile ProteinsFilaminsGlucoseHeterocyclic Compounds, 3-RingInsulinMicrofilament ProteinsMK 2206Proto-Oncogene Proteins c-aktReceptor, Insulin

Identifiers

PMID22846604
PMCPMC3444632
OpenAlexW2034069326

What Socratic holds

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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.