Prototypes for developing new safer medicines effective against type II diabetes have been created by the scientists from Dana-Farber Cancer Institute in Boston and the Scripps Research Institute in Jupiter, Fla. The research which was published in the September 4 issue of the journal “Nature” claims that these prototype drugs have powerful anti-diabetic effect and when tested in mice, were found to be free of the dangerous side effects of the presently available medications. Important anti diabetic medicines like rosiglitazone (Avandia) and pioglitazone (Actos), members of drug class called thiazolidinediones (TZD), can produce fatal weight gain or fluid retention. In certain patients, Avandia and Actos have been associated with fatal heart attacks and loss of bone density. However, these side effects were not produced in diabetes prone mice while testing one of the new prototypes.
TZD medicines act by targeting PPAR-gamma, a transcription factor which affects fat cell development and is related to development of diabetes. The new prototypes also target PPAR-gamma but through a different mechanism. Bruce Spiegelman of Dana-Farber and Patrick Griffin, PhD, of Scripps, who led the research found that PPAR-gamma acts by producing certain changes in genes which improve cells’ response to insulin and help the body to control blood sugar. But these changes also result in the harmful fluid retention, weight gain, and loss of bone density. They also found a second mechanism of action of TZD drugs, which was by blocking a process called as phosphorylation. This second mechanism was found to be free of the side effects produced in the first mechanism. The researchers devised prototype drugs which produce their anti-diabetic action by blocking the phosphorylation of PPAR-gamma.
The new prototypes have been tested in overfed and genetically obese mice prone to diabetes and were found to be devoid of the side effects normally associated with the TZD class of anti-diabetic drugs. The research has shown that it is feasible to make new anti-diabetic drugs which will be safer as compared to the present crop of medicines.