ERC funds DiaDrug project to study the link between insulin resistance and albuminuria

Academy Research Fellow Sanna Lehtonen from the University of Helsinki has received the ERC Starting Grant for her research on kidney diseases. The funding will be up to 2 million euro for up to five years.

The European Research Council (ERC) expects to fund some 240 top researchers in its second prestigious ERC Starting Grant competition. This new wave of grantees follows the 299 researchers who received grants in the first Starting Grant competition in 2007. In total, 2503 proposals were submitted to the second Starting Grant call.

Sanna Lehtonen's research group is studying the kidney glomerular ultrafiltration in both health and under pathological conditions, concentrating especially on studying the development of albuminuria that is an indicator of kidney disease. "Specifically, we are interested in the pathophysiological mechanisms leading to the development of diabetic nephropathy, a serious complication of diabetes", Lehtonen says.

Up to one third of diabetic patients develop nephropathy. Microalbuminuria is the earliest sign of the complication, which may ultimately develop into end-stage renal disease requiring dialysis or a kidney transplant. Insulin resistance has been associated with an increased risk for diabetic nephropathy. "Interestingly, glomerular epithelial cells or podocytes have recently been found to be insulin responsive and to increase their glucose uptake upon insulin stimulation. It has also been shown that intact filamentous actin cytoskeleton is required for the insulin response. Our studies concentrate on analyzing the role of insulin signaling and glucose transport and the regulation of actin cytoskeleton in podocytes thereby aiming to define the mechanisms leading to perturbations in the kidney ultrafiltration function and development of albuminuria", Lehtonen tells.

The aim of Lehtonen's ERC project called DiaDrug is to clarify the mechanisms leading to the development of insulin resistance in podocytes and to study the association between insulin resistance and the development of albuminuria. The researchers will develop transgenic zebrafish and mouse models to study the role of proteins associated with insulin signaling in podocytes, both under normal and pathologic conditions.

"Further, we aim to identify novel drug leads to treat insulin resistance 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 nephropathy in diabetic patients", Lehtonen says.

Sanna Lehtonen started her studies on kidney already during the early 1990's as a PhD student. Her thesis project was on developmental biology, and in particular, about identifying and characterizing novel genes associated with epithelial cell differentiation in the kidney. Later her studies have turned more in the direction of kidney diseases and most recently concentrated on analyzing the development of albuminuria during the development of diabetic nephropathy.

"Diabetes is increasing at an alarming rate worldwide. Renal complication is the most serious of its complications and is also associated with an increased risk of cardiovascular disease. Treating diabetes consumes a large bulk of the healthcare costs in all countries, and therefore understanding the mechanisms leading to the development of the complications, especially nephropathy, identifying it at an earlier stage and finding novel drug targets and drugs to prevent the progression of the complication are currently under intensive research", Lehtonen states.

"Receiving the ERC grant was really fantastic news for me. Now we can finally do some things that we were earlier able to only think and dream about", Lehtonen says.