Metabolic Effects of the Biguanides and Possible Mechanism of Action

Publisher Website
Google Scholar
Abstract
The relationship between the biguanide inhibition of oxidations and their effect on glucose metabolism in vitro was investigated. A good correlation between the concentration of biguanide causing a half-maximal inhibition of pyruvate oxidation (Ki) and the concentration eliciting a half-maximal stimulation (Ks) of glucose uptake in several tissues from rat, guinea pig and pigeon. Guinea pig epididymal fat pad was the most sensitive tissue tested. Gluconeogenesis by minced guinea pig liver was inhibited by the biguan ides. The ability of the biguanides to inhibit gluconeogenesis correlated well with their ability to inhibit pyruvate oxidation. Inhibition of oxidations by the biguanides does not appear to be a result of a direct inhibition of the enzymes catalyzing these oxidations but seems to be secondary to a primary effect on the coupled processes of electron transport and oxidative phosphorylation. Objections to the theory that the metabolic actions of the biguanides are a result of their inhibition of oxidative processes are discussed. The inhibition of oxidations caused by the biguanides is directly related to their metabolic and hypoglycemic effects.