Analysis of the inhibitory effect of biguanides on glucose absorption: Inhibition of active sugar transport

Abstract

The effect of biguanides (phenethylbiguanide, butylbiguanide and dimethylbiguanide) on absorption of actively transported sugars was examined by incubating rings of hamster small intestine in vitro. Biguanides inhibited transport of D-glucose, D-galactose and 3-0-methyl-D-glucose but had no effect on the transport of D-fructose. Inhibition of D-xylose transport could only be demonstrated if concentrations far below halfmaximal saturation concentration (Km) were used (10-5M), but not with concentrations approaching concentrations during a D-xylose tolerance test (18 mM). Formation of lactate by intestinal tissue was increased in presence of biguanides using D-glucose or D-fructose as substrates. The minimal inhibitory concentrations on transport of D-galactose were 10-3M for phenethylbiguanide, 2×10-3M for butylbiguanide and 6×10-3M for dimethylbiguanide. The metabolite of phenethylbiguanide, 1-(4-hydroxy-β-phenethyl)-biguanide, did not affect glucose uptake but increased glucose metabolism to some extent. The demonstrated inhibition of active intestinal transport in vitro may be the mechanism for the decreased absorption of glucose observed by other authors in vivo in man and animals after biguanides. © 1971 Springer-Verlag.