| Selby PL, Sherratt HS (1989) Substituted 2-oxiranecarboxylic acids: a new group of candidate hypoglycaemic drugs. Trends Pharmacol Sci 10:495-500. |
Selby PL, Sherratt HS (1989) Trends Pharmacol Sci
Abstract: Drugs to treat diabetes that can be taken orally have long been sought, although the successful management of insulin-dependent diabetes mellitus by simple chemotherapy may be an unachievable goal. The only drugs currently used for the treatment of non-insulin-dependent diabetes have limited effectiveness. In this article Peter Selby and Stanley Sherratt describe the development of a new group of candidate hypoglycaemic drugs, esters of substituted 2-oxiranecarboxylic acids, which merit full clinical evaluation. These drugs are hydrolysed to the free acids which are then converted to their coenzyme A esters in cells. The CoA esters inactivate carnitine palmitoyltransferase I in the outer mitochondrial membrane, thus preventing the excessive oxidation of long-chain fatty acids that occurs in diabetes. This causes a secondary decrease in hepatic gluconeogenesis and an increase in peripheral glucose utilization leading to improved glucose tolerance.
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