La découverte des propriétés glycosuriques de la phloridzine

The glycosuric effect of phlorizin, the ancestor of the inhibitors of type 2 sodium-glucose cotransporters (SGLT-2) has been described by Joseph von Mering in 1886, 3 years before his discovery, with Oskar Minkowski, of the pancreatic origin of diabetes. The molecule, isolated in 1835 by two Belgian chemists, L.-G. De Koninck and J.-S. Stas, has been initially considered as an antipyretic and antiinfectious agent. The first experimental works, done for a large part in Strasbourg by von Mering and several of his colleagues and assistants, have established that the effect of the drug was independent from the pancreas, the liver and the nervous system, and that the kidney was its unique or at least essential site of action. These works were however not able to determine its precise mechanism of action, which will only be clarified in 1930 and definitely in the 90s when the SGLT receptors were discovered. Although the experiments with phlorizin brought an answer to several physiologic and pathophysiologic questions, the possibility of its therapeutic use has not been evoked at that time, despite of the apparent absence of major toxic effects.