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Content archived on 2024-05-28

Insulin resistance and diabetic nephropathy - development of novel in vivo models for drug discovery

Objective

Up to one third of diabetic patients develop nephropathy, a serious complication of diabetes. Microalbuminuria is the earliest sign of the complication, which may ultimately develop to end-stage renal disease requiring dialysis or a kidney transplant. Insulin resistance and metabolic syndrome are associated with an increased risk for diabetic nephropathy. Interestingly, glomerular epithelial cells or podocytes have recently been shown to be insulin responsive. Further, nephrin, a key structural component of podocytes, is essential for insulin action in these cells. Our novel findings show that adaptor protein CD2AP, an interaction partner of nephrin, associates with regulators of insulin signaling and glucose transport in glomeruli. The results suggest that nephrin and CD2AP are involved, by association with these proteins, in the regulation of insulin signaling and glucose transport in podocytes. We hypothesize that podocytes can develop insulin resistance and that disturbances in insulin response affect podocyte function and contribute to the development of diabetic nephropathy. The aim of this project is to clarify the mechanisms leading to development of insulin resistance in podocytes and to study the association between insulin resistance and the development of diabetic nephropathy. For this we will develop transgenic zebrafish and mouse models by overexpressing/knocking down insulin signaling-associated proteins specifically in podocytes. Further, we aim to identify novel drug leads to treat insulin resistance and diabetic nephropathy by performing high-throughput small molecule library screens on the developed transgenic fish models. The ultimate goal is to find a treatment to combat the early stages of diabetic nephropathy in humans.

Call for proposal

ERC-2009-StG
See other projects for this call

Host institution

HELSINGIN YLIOPISTO
EU contribution
€ 2 000 000,00
Address
YLIOPISTONKATU 3
00014 Helsingin Yliopisto
Finland

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Region
Manner-Suomi Helsinki-Uusimaa Helsinki-Uusimaa
Activity type
Higher or Secondary Education Establishments
Principal investigator
Sanna Lehtonen (Dr.)
Administrative Contact
Kaisa Ainala (Ms.)
Links
Total cost
No data

Beneficiaries (1)