The role of insulin signaling pathway on the development of diabetic nephropathy

2016 Fiscal Year Final Research Report

• Project/Area Number: 26670455
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: National Center for Global Health and Medicine
• Principal Investigator: Kaburagi Yasushi 国立研究開発法人国立国際医療研究センター, その他部局等, 臓器障害研究部長 (40342927)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 糸球体上皮細胞 / インスリンシグナル伝達系

Outline of Final Research Achievements

In this study, we examined the role of insulin signaling pathway in podocytes on the development of diabetic nephropathy. The podocyte-specific knock-out mice were generated using the Cre-mediated recombination controlled by the podocin promoter. Knock-out mice was developed proteinuria around 3 week-old age, and died due to end stage renal failure by 10 weeks after birth. Histologically, features characteristic of focal segmental glomerular sclerosis, including podocyte foot process effacement, mesangial sclerosis, and casts, were observed in the kidney of knock-out mice. Podocytes isolated from knockout-mice also exhibited the lowered autophagic activity as indicated by an increased abundance of p62 and a decreased abundance of LC3B-II. These findings suggest that dysregulation of insulin signaling pathway in podocytes may be involved in the pathogenesis of podocyte injury, leading to proteinuric kidney disease.

Free Research Field

糖尿病学