New candidate for prevention of type 2 daiabetes focus on skeletal muscle glucose metabolism signaling

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K11466
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59020:Sports sciences-related
• Research Institution: Kobe University
• Principal Investigator: Sato Koji 神戸大学, 人間発達環境学研究科, 准教授 (20584022)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 糖尿病 / 骨格筋 / 糖代謝

Outline of Final Research Achievements

The aim of the present study was to investigate the effects of OSMR subunit gp130 knockdown on insulin-stimulated glucose metabolism-related signaling pathways and glucose uptake in skeletal muscle cells. siRNA-mediated gp130 knockdown was conducted in C2C12 muscle cells, and insulin was added and incubated for 1 h. The cells were cultivated to analyze the mRNA levels of gp130, phosphorylation of STAT3, and glucose metabolism-regulated signaling pathways, and OSM levels in the culture medium were analyzed. PI3-kinase activity and Akt Thr 308 phosphorylation were significantly decreased in gp130-/-. The insulin-stimulated increase in glucose uptake rate was significantly attenuated in gp130-/-. In the culture medium, OSM levels were significantly lower in gp130+/+ compared to gp130-/- cell. In conclusion, the knockdown of gp130 caused a decrease in STAT 3 phosphorylation and resulted in the attenuation of insulin-mediated glucose metabolism signaling in skeletal muscle cells.

Free Research Field

健康科学

Academic Significance and Societal Importance of the Research Achievements

本研究では、運動トレーニングによる2型糖尿病予防に向けた新規骨格筋糖代謝調節経路を確立するために、OSMRサブユニットgp130の遺伝子欠損がSTAT3の活性を抑制し骨格筋糖代謝調節経路の活性を抑制するか否かを明らかにすることを目的とした。これまで、OSMの過剰発現は癌細胞の増殖や、肝疾患、自己免疫疾患の発症に関連するという報告がなされてきたが、2型糖尿病における骨格筋糖代謝不全との関連を示す研究は行われてこなかった。本研究で、新規の骨格筋糖代謝調節機構を同定し、さらに、本研究の結果から、今後、肥満症や2型糖尿病発症予防に向けた、運動・栄養介入法の分子基盤が確立される可能性がある。