IRS1/insulin signaling-induced repair mechanisms of podocyte injury

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461230
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Kindai University
• Principal Investigator: MIMA Akira 近畿大学, 医学部附属病院, 講師 (00432401)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: インスリンシグナル / ポドサイトアポトーシス / IRS1

Outline of Final Research Achievements

Immunoblot analyses showed insulin (10nM) increased the levels of phosphorylation of Akt (pAkt) which had anti-apoptotic effects by 4.5±0.7-fold. In contrast, high glucose (HG; 20mM) levels decreased the expression by 7.8%. Insulin increased tyrosine phosphorylation of insulin substrate (IRS)1 by 2-fold in low glucose (LG; 5.6mM), while HG decreased the expression by 10%. Infection with IRS1 using adenoviral vector (Ad-IRS1) decreased HG-induced podocyte apoptosis by 57%. To assess the role of IRS1 in mediating the podocyte apoptosis, IRS1 expression was reduced with siIRS1. Knockdown of IRS1 in podocytes increased apoptosis by 2.4±0.4-fold. Lastly, DPP-4 inhibitor increased the levels of pAkt by 131±28%. These results suggest that increases in insulin signaling activity in podocytes using Ad-IRS1 or DPP-4i could inhibit HG-induced podocyte apoptosis.

Free Research Field

糖尿病性腎症