Cardiac corin and atrial natriuretic peptide regulate liver glycogen metabolism and glucose homeostasis.
Animals
Atrial Natriuretic Factor
/ metabolism
Mice, Knockout
Homeostasis
Hepatocytes
/ metabolism
Signal Transduction
Humans
Serine Endopeptidases
/ metabolism
Liver Glycogen
/ metabolism
Liver
/ metabolism
Mice, Inbred C57BL
Proto-Oncogene Proteins c-akt
/ metabolism
Cells, Cultured
Glucose
/ metabolism
Blood Glucose
/ metabolism
Cyclic GMP-Dependent Protein Kinases
/ metabolism
Mice
Male
Myocardium
/ metabolism
ANP
Corin
Glucose homeostasis
Hepatocytes
Liver glycogen metabolism
PKG signaling
Journal
Cardiovascular diabetology
ISSN: 1475-2840
Titre abrégé: Cardiovasc Diabetol
Pays: England
ID NLM: 101147637
Informations de publication
Date de publication:
28 Oct 2024
28 Oct 2024
Historique:
received:
02
08
2024
accepted:
15
10
2024
medline:
29
10
2024
pubmed:
29
10
2024
entrez:
29
10
2024
Statut:
epublish
Résumé
Cardiovascular function and metabolic homeostasis are closely linked, but the underlying mechanisms are not fully understood. Corin is a protease that activates atrial natriuretic peptide (ANP), an essential hormone for normal blood pressure and cardiac function. The goal of this study is to investigate a potential corin and ANP function in regulating liver glycogen metabolism and glucose homeostasis. Liver glycogen and blood glucose levels were analyzed in Corin or Nppa (encoding ANP) knockout (KO) mice. ANP signaling was examined in livers from Corin and Nppa KO mice and in cultured human and mouse hepatocytes by western blotting. We found that Corin and Nppa KO mice had reduced liver glycogen contents and increased blood glucose levels. By analyzing conditional KO mice lacking either cardiac or renal Corin, we showed that cardiac corin and ANP act in an endocrine manner to enhance cGMP-protein kinase G (PKG)-AKT-GSK3 signaling in hepatocytes. In cultured hepatocytes, ANP treatment stimulated PKG signaling, glucose uptake, and glycogen production, which could be blocked by small molecule PKG and AKT inhibitors. Our results indicate that corin and ANP are important regulators in liver glycogen metabolism and glucose homeostasis, suggesting that defects in the corin and ANP pathway may contribute to both cardiovascular and metabolic diseases.
Sections du résumé
BACKGROUND
BACKGROUND
Cardiovascular function and metabolic homeostasis are closely linked, but the underlying mechanisms are not fully understood. Corin is a protease that activates atrial natriuretic peptide (ANP), an essential hormone for normal blood pressure and cardiac function. The goal of this study is to investigate a potential corin and ANP function in regulating liver glycogen metabolism and glucose homeostasis.
METHODS
METHODS
Liver glycogen and blood glucose levels were analyzed in Corin or Nppa (encoding ANP) knockout (KO) mice. ANP signaling was examined in livers from Corin and Nppa KO mice and in cultured human and mouse hepatocytes by western blotting.
RESULTS
RESULTS
We found that Corin and Nppa KO mice had reduced liver glycogen contents and increased blood glucose levels. By analyzing conditional KO mice lacking either cardiac or renal Corin, we showed that cardiac corin and ANP act in an endocrine manner to enhance cGMP-protein kinase G (PKG)-AKT-GSK3 signaling in hepatocytes. In cultured hepatocytes, ANP treatment stimulated PKG signaling, glucose uptake, and glycogen production, which could be blocked by small molecule PKG and AKT inhibitors.
CONCLUSIONS
CONCLUSIONS
Our results indicate that corin and ANP are important regulators in liver glycogen metabolism and glucose homeostasis, suggesting that defects in the corin and ANP pathway may contribute to both cardiovascular and metabolic diseases.
Identifiants
pubmed: 39468553
doi: 10.1186/s12933-024-02475-w
pii: 10.1186/s12933-024-02475-w
doi:
Substances chimiques
Atrial Natriuretic Factor
85637-73-6
Corin protein, mouse
EC 3.4.21.-
Serine Endopeptidases
EC 3.4.21.-
Liver Glycogen
0
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Glucose
IY9XDZ35W2
CORIN protein, human
EC 3.4.21.-
Blood Glucose
0
Cyclic GMP-Dependent Protein Kinases
EC 2.7.11.12
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
383Subventions
Organisme : Boxi Youth Natural Science Foundation
ID : BXQN2023020
Organisme : Interdisciplinary Basic Frontier Innovation Program of Suzhou Medical College of Soochow University
ID : YXY2304065
Organisme : National Natural Science Foundation of China
ID : 32171112
Informations de copyright
© 2024. The Author(s).
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