PMID- 32439824
OWN - NLM
STAT- MEDLINE
DCOM- 20201218
LR  - 20210812
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 69
IP  - 8
DP  - 2020 Aug
TI  - Reciprocity Between Skeletal Muscle AMPK Deletion and Insulin Action in 
      Diet-Induced Obese Mice.
PG  - 1636-1649
LID - 10.2337/db19-1074 [doi]
AB  - Insulin resistance due to overnutrition places a burden on energy-producing 
      pathways in skeletal muscle (SkM). Nevertheless, energy state is not compromised. 
      The hypothesis that the energy sensor AMPK is necessary to offset the metabolic 
      burden of overnutrition was tested using chow-fed and high-fat (HF)-fed 
      SkM-specific AMPKalpha1alpha2 knockout (mdKO) mice and AMPKalpha1alpha2lox/lox littermates 
      (wild-type [WT]). Lean mdKO and WT mice were phenotypically similar. HF-fed mice 
      were equally obese and maintained lean mass regardless of genotype. Results did 
      not support the hypothesis that AMPK is protective during overnutrition. 
      Paradoxically, mdKO mice were more insulin sensitive. Insulin-stimulated SkM 
      glucose uptake was approximately twofold greater in mdKO mice in vivo. 
      Furthermore, insulin signaling, SkM GLUT4 translocation, hexokinase activity, and 
      glycolysis were increased. AMPK and insulin signaling intersect at mammalian 
      target of rapamycin (mTOR), a critical node for cell proliferation and survival. 
      Basal mTOR activation was reduced by 50% in HF-fed mdKO mice, but was normalized 
      by insulin stimulation. Mitochondrial function was impaired in mdKO mice, but 
      energy charge was preserved by AMP deamination. Results show a surprising 
      reciprocity between SkM AMPK signaling and insulin action that manifests with 
      diet-induced obesity, as insulin action is preserved to protect fundamental 
      energetic processes in the muscle.
CI  - (c) 2020 by the American Diabetes Association.
FAU - Lantier, Louise
AU  - Lantier L
AUID- ORCID: 0000-0002-6620-4976
AD  - Department of Molecular Physiology and Biophysics, Vanderbilt University School 
      of Medicine, Nashville, TN louise.lantier@vanderbilt.edu.
AD  - Vanderbilt Mouse Metabolic Phenotyping Center, Nashville, TN.
FAU - Williams, Ashley S
AU  - Williams AS
AD  - Department of Molecular Physiology and Biophysics, Vanderbilt University School 
      of Medicine, Nashville, TN.
FAU - Williams, Ian M
AU  - Williams IM
AD  - Department of Molecular Physiology and Biophysics, Vanderbilt University School 
      of Medicine, Nashville, TN.
FAU - Guerin, Amanda
AU  - Guerin A
AD  - Department of Molecular Physiology and Biophysics, Vanderbilt University School 
      of Medicine, Nashville, TN.
FAU - Bracy, Deanna P
AU  - Bracy DP
AD  - Department of Molecular Physiology and Biophysics, Vanderbilt University School 
      of Medicine, Nashville, TN.
FAU - Goelzer, Mickael
AU  - Goelzer M
AD  - Department of Molecular Physiology and Biophysics, Vanderbilt University School 
      of Medicine, Nashville, TN.
FAU - Foretz, Marc
AU  - Foretz M
AD  - Universite de Paris, Institut Cochin, CNRS, INSERM, Paris, France.
FAU - Viollet, Benoit
AU  - Viollet B
AD  - Universite de Paris, Institut Cochin, CNRS, INSERM, Paris, France.
FAU - Hughey, Curtis C
AU  - Hughey CC
AD  - Department of Molecular Physiology and Biophysics, Vanderbilt University School 
      of Medicine, Nashville, TN.
FAU - Wasserman, David H
AU  - Wasserman DH
AD  - Department of Molecular Physiology and Biophysics, Vanderbilt University School 
      of Medicine, Nashville, TN.
AD  - Vanderbilt Mouse Metabolic Phenotyping Center, Nashville, TN.
LA  - eng
SI  - figshare/10.2337/figshare.12328136
GR  - R37 DK050277/DK/NIDDK NIH HHS/United States
GR  - F31 DK109594/DK/NIDDK NIH HHS/United States
GR  - P30 DK058404/DK/NIDDK NIH HHS/United States
GR  - P30 EY008126/EY/NEI NIH HHS/United States
GR  - P30 DK020593/DK/NIDDK NIH HHS/United States
GR  - U24 DK059637/DK/NIDDK NIH HHS/United States
GR  - R01 DK050277/DK/NIDDK NIH HHS/United States
GR  - R56 DK054902/DK/NIDDK NIH HHS/United States
GR  - P30 CA068485/CA/NCI NIH HHS/United States
GR  - R01 DK054902/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20200521
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Glucose Transporter Type 4)
RN  - 0 (Insulin)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinases/*metabolism
MH  - Animals
MH  - Body Composition/physiology
MH  - Body Weight/physiology
MH  - Glucose Transporter Type 4/metabolism
MH  - Hexokinase/metabolism
MH  - Humans
MH  - Insulin/*metabolism
MH  - Insulin Resistance/physiology
MH  - Mice
MH  - Mice, Knockout
MH  - Mice, Obese
MH  - Muscle, Skeletal/*metabolism
MH  - Signal Transduction/genetics/physiology
PMC - PMC7372072
EDAT- 2020/05/23 06:00
MHDA- 2020/12/19 06:00
PMCR- 2021/08/01
CRDT- 2020/05/23 06:00
PHST- 2019/10/24 00:00 [received]
PHST- 2020/05/19 00:00 [accepted]
PHST- 2020/05/23 06:00 [pubmed]
PHST- 2020/12/19 06:00 [medline]
PHST- 2020/05/23 06:00 [entrez]
PHST- 2021/08/01 00:00 [pmc-release]
AID - db19-1074 [pii]
AID - 191074 [pii]
AID - 10.2337/db19-1074 [doi]
PST - ppublish
SO  - Diabetes. 2020 Aug;69(8):1636-1649. doi: 10.2337/db19-1074. Epub 2020 May 21.