Abstract
The antidiabetic biguanide metformin has been shown to increase faecal excretion of bile salts in type 2 diabetes. Cultured human intestinal Caco-2 cell monolayers provide a model of human enterocytes. These monolayers are used here to determine the effect of metformin on the secondary-active, sodium-linked transfer of 14C-glycocholate from the apical (brush border) to the basolateral (serosal) surface. During 24-h incubations, 10-2 mol/l metformin significantly reduced 14C-glycocholate transfer. This could not be attributed to alterations of monolayer integrity or Na+-K+ ATPase pump activity. For example, the secondary-active transport of glucose and proline was not interrupted, and the inhibitory effect of metformin on bile salt transport was additive to the inhibitory effect of ouabain. The results suggest that metformin can act directly on intestinal enterocytes to reduce the active transfer of bile salts by a mechanism that is independent of Na+-K+ ATPase activity.
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