Role of p110a subunit of PI3-kinase in skeletal muscle mitochondrial homeostasis and metabolism.
Animals
Class I Phosphatidylinositol 3-Kinases
/ genetics
Homeostasis
Insulin
/ metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mitochondria
/ enzymology
Muscle, Skeletal
/ enzymology
NAD
/ metabolism
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
/ genetics
Phosphatidylinositol 3-Kinases
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
30 07 2019
30 07 2019
Historique:
received:
06
12
2017
accepted:
02
07
2019
entrez:
1
8
2019
pubmed:
1
8
2019
medline:
19
12
2019
Statut:
epublish
Résumé
Skeletal muscle insulin resistance, decreased phosphatidylinositol 3-kinase (PI3K) activation and altered mitochondrial function are hallmarks of type 2 diabetes. To determine the relationship between these abnormalities, we created mice with muscle-specific knockout of the p110α or p110β catalytic subunits of PI3K. We find that mice with muscle-specific knockout of p110α, but not p110β, display impaired insulin signaling and reduced muscle size due to enhanced proteasomal and autophagic activity. Despite insulin resistance and muscle atrophy, M-p110αKO mice show decreased serum myostatin, increased mitochondrial mass, increased mitochondrial fusion, and increased PGC1α expression, especially PCG1α2 and PCG1α3. This leads to enhanced mitochondrial oxidative capacity, increased muscle NADH content, and higher muscle free radical release measured in vivo using pMitoTimer reporter. Thus, p110α is the dominant catalytic isoform of PI3K in muscle in control of insulin sensitivity and muscle mass, and has a unique role in mitochondrial homeostasis in skeletal muscle.
Identifiants
pubmed: 31363081
doi: 10.1038/s41467-019-11265-y
pii: 10.1038/s41467-019-11265-y
pmc: PMC6667496
doi:
Substances chimiques
Insulin
0
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
0
NAD
0U46U6E8UK
1-phosphatidylinositol 3-kinase p110 subunit, mouse
EC 2.7.1.137
Class I Phosphatidylinositol 3-Kinases
EC 2.7.1.137
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
3412Subventions
Organisme : NIDDK NIH HHS
ID : K01 DK120740
Pays : United States
Organisme : NIDDK NIH HHS
ID : K08 DK100543
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK055545
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK007260
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK036836
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK033201
Pays : United States
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