G0S2 in liver regulates insulin sensitivity

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09363
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Juntendo University
• Principal Investigator: SATOH HIROAKI 順天堂大学, 医学部, 先任准教授 (20323595)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 脂肪肝 / インスリン抵抗性 / 糖尿病 / G0S2

Outline of Final Research Achievements

We investigated the effects of hepatic G0S2 on insulin sensitivity in male Wistar rats receiving a normal chow diet (NCD) or a high-fat diet (HFD). In the HFD-fed rats, during the clamp study, the glucose infusion rate required for euglycemia significantly decreased by 16% in the Ad-G0S2 group compared with the Ad-GFP group. The insulin-suppressed hepatic glucose output significantly increased in the Ad-G0S2 group. Moreover, Oil Red O-staining indicated that overexpression of G0S2 protein in the liver promoted hepatic steatosis by 2.5-fold in the HFD-fed rats. However, Masson’s trichrome staining revealed that overexpression of G0S2 significantly ameliorated fibrosis in the livers of the HFD-fed rats. Consistent with histological data, the expression of TGF-b and Smad2 were significantly decreased in livers of the HFD-fed rats.
These results indicate that hepatic G0S2 protein might promote hepatic insulin resistance by exacerbating hepatic steatosis, but ameliorating hepatic fibrosis.

Free Research Field

消化器内科

Academic Significance and Societal Importance of the Research Achievements

本研究では、肝臓でのG0S2蛋白発現が脂肪肝の進展に関与し、肝臓でのインスリン抵抗性の増悪因子としての役割を果たすことを明らかにした。
本研究の成果により、肝臓におけるG0S2蛋白と脂肪肝・インスリン抵抗性との関連が解明され、インスリン抵抗性の新たな発症機序の解明につながると期待される。さらに今後ますます重要と考えられるインスリン抵抗性の治療薬の開発につながると期待される。