Cardiovasc Diabetol. 2024 Oct 28;23(1):383.  doi: 10.1186/s12933-024-02475-w

题目：

Cardiac corin and atrial natriuretic peptide regulate liver glycogen metabolism and glucose homeostasis.

作者：

Wenguo Li^1,2†, Xianrui Zhang^1,2†, Zibin Zhou^2,3†, Wenjun Guo^1,2, Mengting Wang^1,2, Tiantian Zhou², Meng Liu², Qingyu Wu^2* and Ningzheng Dong^1,2*

单位：

¹Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Suzhou Medical College, Soochow University, Suzhou, China

²Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Soochow University, Suzhou, China

³Department of Orthopedics, the Second Affiliated Hospital of Soochow University, Suzhou, China

摘要：

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: 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: 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: 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.