Abstract
In previous reports we showed that certain hypoglycemic agents (phenformin, tolbutamide, chlorpropamide) inhibit specific enzymic steps of cholesterol synthesis, and we used these agents to define pathways and intermediates of cholesterol biosynthesis (1,2). The purpose of this report is to describe recent data offering new insights into the mechanism of action of these drugs on the molecular events of cholesterol biosynthesis. Most of these studies were performed with phenformin and related biguanides (buformin and the hydroxy-derivative of phenformin) known to be effective hypoglycemic agents. The data were obtained using synthetic labeled cholesterol precursors as substrates for an enzyme system catalyzing cholesterol synthesis which we recently purified from rat liver (3). It is hoped that these studies in vitro will lead to an improved understanding of the hypoglycemic and hypolipidemic effects observed in vivo during treatment of diabetics with biguanides (4).
Supported by U.S.P.H.S. Research Grants HE-8634 and HE-6314
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Dempsey, M.E. (1969). The Effect of Hypoglycemic Agents on Cholesterol Biosynthesis. In: Holmes, W.L., Carlson, L.A., Paoletti, R. (eds) Drugs Affecting Lipid Metabolism. Advances in Experimental Medicine and Biology, vol 4. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-6866-7_42
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DOI: https://doi.org/10.1007/978-1-4615-6866-7_42
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