Research Holds Promise For Novel Oral Anti-diabetic Drugs

For his groundbreaking work, Prof. Shlomo Sasson of the Hebrew University School of Pharmacy has been named one of the winners this year of the Hebrew University's Kaye Innovation Awards.

Type 2 diabetes is a worldwide epidemic, predicted to affect over 380 million people within the next 20 years. This disease is characterized by high blood glucose levels that lead to severe complications in various organs and tissues. The disease usually results from insufficient secretion and function of the pancreatic hormone insulin that regulates glucose metabolism in peripheral tissues, such as skeletal muscles, fatty tissues and the liver.

Pharmacological anti-diabetic therapy aims at a strict regulation of blood glucose levels to prevent such complications. However, because current oral anti-diabetic drugs often fail, many patients need daily injections of insulin to control their glucose metabolism and reduce blood glucose levels.

The global diabetes therapy market is estimated at around US$26.3 billion in 2009. By 2013 the market is expected to grow to around US$34.5 billion.

Recent work on the molecular mechanisms that regulate glucose transport in skeletal muscles has identified new potential targets for anti-diabetic drugs.

In his research, Sasson, with his colleagues and students, made a unique discovery that high levels of the carbohydrate D-xylose increased the rate of glucose entry into skeletal muscle cells in a non-insulin-dependent manner. They then used it as a prototype molecule for the planning and synthesis of chemical derivatives that may act as potential drugs to lower blood glucose in type 2 diabetic patients.

Some of these derivatives increased significantly the rate of glucose transport in skeletal muscles at very low concentrations. This effect was not achieved by mimicking the classical pathway of insulin action, but by activating the enzyme AMP-activated protein kinase (AMPK). When activated, this enzyme increases the rate of glucose transport in skeletal muscles in the absence of insulin. Therefore, compounds that activate this enzyme can be effective in insulin resistant type 2 diabetic patients or in those that fail to respond to conventional drug therapy. This makes AMPK an extremely attractive target in the development of novel anti-diabetic drugs.

One of the lead compounds developed by Sasson and colleagues effectively reduced blood glucose levels in various animal models of diabetes. This discovery indicates the great potential of these novel derivatives to serve as the basis for development of new drugs to normalize blood glucose levels in diabetic patients.