Role of PKG/VASP signaling on glucose metabolism

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09414
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Kobe University
• Principal Investigator: TATEYA SANSHIRO 神戸大学, 医学研究科, 医学研究員 (70639260)
• Co-Investigator(Kenkyū-buntansha): 田守 義和 神戸大学, 医学研究科, 客員教授 (90379397)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: インスリン抵抗性 / 一酸化窒素

Outline of Final Research Achievements

We show that high-fat feeding induces proinflammatory activation of Kupffer cells in wild-type mice coincident with reduced liver endothelial nitric oxide synthase activity and NO content while, conversely, enhancement of signaling downstream of endogenous NO by phosphodiesterase-5 inhibition protects against high fat-induced inflammation in Kupffer cells. Furthermore, proinflammatory activation of Kupffer cells is evident in eNos(-/-) mice even on a low-fat diet. These results collectively imply a physiological role for endothelial NO to limit obesity-associated inflammation and insulin resistance in hepatocytes and support a model in which Kupffer cell activation during high-fat feeding is dependent on reduced NO signaling. Our findings also identify the NO/VASP pathway as a novel potential target for the treatment of obesity-associated liver insulin resistance.

Free Research Field

糖尿病