Apolipoprotein J is a hepatokine regulating muscle glucose metabolism and insulin sensitivity.
Adult
Animals
Cell Line
Clusterin
/ blood
Disease Models, Animal
Female
Glucose
/ metabolism
Glucose Clamp Technique
Humans
Hypoglycemic Agents
/ pharmacology
Insulin
/ metabolism
Insulin Resistance
Liver
/ metabolism
Low Density Lipoprotein Receptor-Related Protein-2
/ genetics
Male
Mice
Mice, Knockout
Muscle, Skeletal
/ metabolism
Pioglitazone
/ pharmacology
Polycystic Ovary Syndrome
/ blood
Receptor, Insulin
/ metabolism
Signal Transduction
/ drug effects
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
24 04 2020
24 04 2020
Historique:
received:
21
02
2018
accepted:
02
04
2020
entrez:
26
4
2020
pubmed:
26
4
2020
medline:
11
8
2020
Statut:
epublish
Résumé
Crosstalk between liver and skeletal muscle is vital for glucose homeostasis. Hepatokines, liver-derived proteins that play an important role in regulating muscle metabolism, are important to this communication. Here we identify apolipoprotein J (ApoJ) as a novel hepatokine targeting muscle glucose metabolism and insulin sensitivity through a low-density lipoprotein receptor-related protein-2 (LRP2)-dependent mechanism, coupled with the insulin receptor (IR) signaling cascade. In muscle, LRP2 is necessary for insulin-dependent IR internalization, an initial trigger for insulin signaling, that is crucial in regulating downstream signaling and glucose uptake. Of physiologic significance, deletion of hepatic ApoJ or muscle LRP2 causes insulin resistance and glucose intolerance. In patients with polycystic ovary syndrome and insulin resistance, pioglitazone-induced improvement of insulin action is associated with an increase in muscle ApoJ and LRP2 expression. Thus, the ApoJ-LRP2 axis is a novel endocrine circuit that is central to the maintenance of normal glucose homeostasis and insulin sensitivity.
Identifiants
pubmed: 32332780
doi: 10.1038/s41467-020-15963-w
pii: 10.1038/s41467-020-15963-w
pmc: PMC7181874
doi:
Substances chimiques
CLU protein, human
0
Clu protein, mouse
0
Clusterin
0
Hypoglycemic Agents
0
Insulin
0
LRP2 protein, human
0
Low Density Lipoprotein Receptor-Related Protein-2
0
Lrp2 protein, mouse
0
Receptor, Insulin
EC 2.7.10.1
Glucose
IY9XDZ35W2
Pioglitazone
X4OV71U42S
Types de publication
Clinical Trial
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
2024Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK111529
Pays : United States
Organisme : CSRD VA
ID : I01 CX000635
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK106076
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK057521
Pays : United States
Commentaires et corrections
Type : ErratumIn
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