Glucose-6-phosphatase inhibitors for the treatment of Type 2 diabetes

Abstract

Much biological knowledge has been gained over the years as to the role of glucose-6-phosphatase, (G-6-pase), enzyme complex in glucose homeostasis and in Type 2 diabetes. Glucose-6-phosphatase is mainly located in the liver and catalyses the terminal step in both gluconeogenesis and glycogenolysis. Another interesting feature is that the enzyme activity is several fold higher in diabetic animals and probably also in diabetic humans and therefore could be an important key player in the elevated hepatic glucose production seen in Type 2 diabetes. During the last nine years substantial efforts have been made, primarily by scientists at Hoechst (now Aventis) and Novo Nordisk, in order to discover novel compounds which inhibit the glucose-6-phosphatase enzyme complex and could be applied therapeutically in the treatment of Type 2 diabetes. These compounds, as well as other compounds published with inhibitory action on glucose-6-phosphatase, are reviewed. No compounds yet have been reported to be in clinical development.

• β
• -cell
• blood glucose homeostasis
• EC 3.1.3.9
• inhibitors
• glucose-6-phosphatase
• T1-translocase
• Type 2 diabetes