Sam68 promotes hepatic gluconeogenesis via CRTC2.
Adaptor Proteins, Signal Transducing
/ genetics
Animals
Blood Glucose
/ metabolism
DNA-Binding Proteins
Diabetes Mellitus, Type 2
/ metabolism
Gene Expression Regulation
Glucagon
/ metabolism
Gluconeogenesis
/ genetics
Glucose
/ metabolism
Hepatocytes
/ metabolism
Homeostasis
Humans
Hyperglycemia
Insulin Resistance
Liver
/ metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
RNA-Binding Proteins
/ genetics
Transcription Factors
/ genetics
Up-Regulation
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
07 06 2021
07 06 2021
Historique:
received:
17
07
2020
accepted:
05
05
2021
entrez:
8
6
2021
pubmed:
9
6
2021
medline:
23
6
2021
Statut:
epublish
Résumé
Hepatic gluconeogenesis is essential for glucose homeostasis and also a therapeutic target for type 2 diabetes, but its mechanism is incompletely understood. Here, we report that Sam68, an RNA-binding adaptor protein and Src kinase substrate, is a novel regulator of hepatic gluconeogenesis. Both global and hepatic deletions of Sam68 significantly reduce blood glucose levels and the glucagon-induced expression of gluconeogenic genes. Protein, but not mRNA, levels of CRTC2, a crucial transcriptional regulator of gluconeogenesis, are >50% lower in Sam68-deficient hepatocytes than in wild-type hepatocytes. Sam68 interacts with CRTC2 and reduces CRTC2 ubiquitination. However, truncated mutants of Sam68 that lack the C- (Sam68
Identifiants
pubmed: 34099657
doi: 10.1038/s41467-021-23624-9
pii: 10.1038/s41467-021-23624-9
pmc: PMC8185084
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Blood Glucose
0
CRTC2 protein, human
0
Crtc2 protein, mouse
0
DNA-Binding Proteins
0
KHDRBS1 protein, human
0
Khdrbs1 protein, mouse
0
RNA-Binding Proteins
0
Transcription Factors
0
Glucagon
9007-92-5
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3340Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL113541
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL138990
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK112934
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK056336
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL131110
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL142291
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL130052
Pays : United States
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