Evidence map›Paper›PMID 21505148›Full record

Trial reportAmerican journal of physiology. Endocrinology and metabolism2011

Exercise increases TBC1D1 phosphorylation in human skeletal muscle.

Niels Jessen, Ding An, Aina S Lihn, Jonas Nygren, Michael F Hirshman, Anders Thorell, Laurie J Goodyear

Open access · greenAbstract readClinical Trial
In one paragraph

Trial report in American journal of physiology. Endocrinology and metabolism, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
4.7field-weighted citation impact, top 5% 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

35 citing papers in PubMed, 66 citations in OpenAlex.

  1. Trial
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  9. Article
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  12. Skeletal muscle cell-specific differences in type 2 diabetes.Cellular and molecular life sciences : CMLS · 2022
    Article
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  15. 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

7 authors at 3 institutions in 3 countries.

Niels JessenJoslin Diabetes Center, Boston, MA 02215, USA.
Ding An
Aina S Lihn
Jonas Nygren
Michael F Hirshman
Anders Thorell
Laurie J Goodyear
Joslin Diabetes Center · USKarolinska Institutet · SEAarhus University Hospital · DK

Funding

SPECIAL ASSAY COREP30DK036836 · NIDDK · JOSLIN DIABETES CENTER · PI JEAN E. SCHAFFER · 1986 to 2026
$50.5M
EXERCISE REGULATION OF GLUCOSE UPTAKE IN SKELETAL MUSCLER01AR045670 · NIAMS · JOSLIN DIABETES CENTER · PI GOODYEAR, LAURIE J · 1998 to 2012
$4.6M
EXERCISE AND SKELETAL MUSCLE SIGNALING MECHANISMSR01AR042238 · NIAMS · JOSLIN DIABETES CENTER · PI GOODYEAR, LAURIE J · 1997 to 2013
$4.2M
NIAMS NIH HHS R01 AR042238NIAMS NIH HHS R01 AR045670NIAMS NIH HHS R01-AR-42238NIAMS NIH HHS R01-AR-45670NIDDK NIH HHS P30-DK-36836
6 · The paper itself

Abstract

Exercise and weight loss are cornerstones in the treatment and prevention of type 2 diabetes, and both interventions function to increase insulin sensitivity and glucose uptake into skeletal muscle. Studies in rodents demonstrate that the underlying mechanism for glucose uptake in muscle involves site-specific phosphorylation of the Rab-GTPase-activating proteins AS160 (TBC1D4) and TBC1D1. Multiple kinases, including Akt and AMPK, phosphorylate TBC1D1 and AS160 on distinct residues, regulating their activity and allowing for GLUT4 translocation. In contrast to extensive rodent-based studies, the regulation of AS160 and TBC1D1 in human skeletal muscle is not well understood. In this study, we determined the effects of dietary intervention and a single bout of exercise on TBC1D1 and AS160 site-specific phosphorylation in human skeletal muscle. Ten obese (BMI 33.4 ± 2.4, M-value 4.3 ± 0.5) subjects were studied at baseline and after a 2-wk dietary intervention. Muscle biopsies were obtained from the subjects in the resting (basal) state and immediately following a 30-min exercise bout (70% Vo(2 max)). Muscle lysates were analyzed for AMPK activity and Akt phosphorylation and for TBC1D1 and AS160 phosphorylation on known or putative AMPK and Akt sites as follows: AS160 Ser(711) (AMPK), TBC1D1 Ser(231) (AMPK), TBC1D1 Ser(660) (AMPK), TBC1D1 Ser(700) (AMPK), and TBC1D1 Thr(590) (Akt). The diet intervention that consisted of a major shift in the macronutrient composition resulted in a 4.2 ± 0.4 kg weight loss (P < 0.001) and a significant increase in insulin sensitivity (M value 5.6 ± 0.6), but surprisingly, there was no effect on expression or phosphorylation of any of the muscle-signaling proteins. Exercise increased muscle AMPKα2 activity but did not increase Akt phosphorylation. Exercise increased phosphorylation on AS160 Ser(711), TBC1D1 Ser(231), and TBC1D1 Ser(660) but had no effect on TBC1D1 Ser(700). Exercise did not increase TBC1D1 Thr(590) phosphorylation or TBC1D1/AS160 PAS phosphorylation, consistent with the lack of Akt activation. These data demonstrate that a single bout of exercise regulates TBC1D1 and AS160 phosphorylation on multiple sites in human skeletal muscle.

Indexed as

AMP-Activated Protein KinasesDietExerciseFemaleGlucose Transporter Type 4GlycogenGTPase-Activating ProteinsHumansIsoenzymesMaleMuscle, SkeletalPhosphorylationProtein IsoformsProtein KinasesProto-Oncogene Proteins c-aktAMP-Activated Protein KinasesGlucose Transporter Type 4GlycogenGTPase-Activating ProteinsIsoenzymesProtein IsoformsProtein KinasesProto-Oncogene Proteins c-aktSLC2A4 protein, humanTBC1D1 protein, humanTBC1D4 protein, human

Identifiers

PMID21505148
PMCPMC3129834
OpenAlexW2169358395

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.