Inhibition of intestinal amino acid transport by blood sugar lowering biguanides

Summary The effect of blood-glucose lowering biguanides (phenethyl- and butylbiguanide) on active intestinal transport of different amino acids has been tested in hamster small intestinein vitro. —.Biguanides inhibited active transport of all amino acids tested. The inhibitory effect of biguanides increased with incubation time, was more pronounced after preincubation of intestinal tissue and was found to be non-competitive. The minimal inhibitory concentration of phenethylbiguanide on amino acid transport was 5×10^–4 M. —¹⁴C-butylbiguanide was found to be transported into hamster small intestine by a concentration-independent, energy-independent uptake mechanism and was accumulated in intestinal tissue against a concentration gradient. — In accord with earlier results on the inhibitory effect of biguanides on active intestinal hexose transport it is concluded that biguanides do not act as specific inhibitors for glucose transport, but rather affect active, energy-requiring intestinal transport mechanisms in general (hexose-, amino acid-, calcium- and myo-inositol transport), most likely due to their known inhibitory effect on mitochondrial respiration, thus depriving mucosal cells of ATP required to translocate substrates against a concentration gradient.Part of this work has been presented at the International Diabetes Congress, Buenos Aires, Argentina, August 1970 and at the Meeting of German and Italian Pharmacology Society, Heidelberg, September 1970.