New Class of Drugs for Type 2 Diabetes

The discovery was reported in the July 18, 2003, issue of Science.

Patients with type 2 diabetes have too little insulin and produce too much glucose. Patients with type 2 diabetes are given two medications to correct these functions. The glucokinase (GK) enzyme breaks down and metabolizes glucose. When the enzyme is functioning properly, it helps the body maintain glucose levels by controlling the release of insulin from the pancreas as well as the disposal of glucose in the liver. Researchers found that GKAs can increase the efficiency of glucokinase and in so doing lower the blood sugar in preclinical models of type 2 diabetics. The GKA compound stimulates the pancreas to release more insulin and also keeps the liver from producing too much glucose.

The GKAs were discovered by scientists at Roche (Basel, Switzerland). Roche's interest in the GK enzyme followed the discovery in 1992 that maturity onset diabetes of the young type 2 (MODY2) is caused by mutations in the GK gene. Preclinical findings provided strong biologic rationale for considering GK as a target for drug discovery. The Roche team screened 120,000 compounds and found one that seemed to activate GK. A test with the early compound proved that GK activation worked.

"By being able to activate the GK enzyme, we may be able to provide a mechanism to improve both defects commonly found in type 2 diabetes, namely insulin release and hepatic glucose metabolism,” said Joseph Grimsby, Ph.D., the author of the Science article and preclinical GKA project leader at Roche.




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