Technique to screen anti-diabetic drugs
doi:10.1038/nindia.2012.140 Published online 25 September 2012
Some compounds inhibit the activity of protein molecules that aid glucose transport and absorption in the small intestine and kidney. Researchers have now formulated a non-radioactive, cell-based screening method to identify these compounds.
The new technique will be useful in identifying novel compounds that inhibit proteins called sodium-dependent glucose cotransporters (SGLTs). These compounds could yield potential drug candidates for treating diabetes and related physiological anomalies.
The human body uses two types of glucose transporters: SGLTs; and sodium-independent facilitative glucose transporters (GLUTs). SGLT2 resorbs the bulk of glucose in kidneys, with the remaining glucose recovered by SGLT1, preventing glucose loss in urine. In diabetes, blood glucose levels are abnormally elevated. Inhibiting SGLT1 and SGLT2 could thus offer a novel and attractive therapeutic strategy to control diabetes. However, simple techniques to identify SGLTs inhibitors are lacking.
To devise a new technique to screen SGLTs inhibitors, the researchers first used bacterial cells to express the genes for SGLT1 and SGLT2. They transferred these genes into human embryonic kidney (HEK) cells, causing the cells to produce SGLTs. The glucose uptake potential of these SGLTs-containing HEK cells was studied and compared with control HEK cells without SGLTs.
The researchers also exposed both forms of HEK cells to a non-specific SGLT inhibitor, phlorizin, to clarify its ability to disrupt SGLT activity.
Almost 2.5-fold increase in glucose uptake was observed in SGLT1- and SGLT2-positive HEK cells compared with controls. When treated with phlorizin, SGLT-containing HEK cells showed a significant decrease in glucose uptake. The SGLT-containing HEK cells were not sensitive to GLUT inhibitors.
The researchers say that unlike other cell-based methods using radioactive compounds, this highly efficient, non-radioactive, cell-based method provides a simple and rapid method for identifying novel and selective SGLT inhibitors.
The authors of this work are from: Division of Pharmacology, and Toxicology Unit, Biology Division, Indian Institute of Chemical Technology, Hyderabad, India.