Inhibition of intestinal absorption and improvement of oral glucose tolerance by biguanides in the normal and in the streptozotocin-diabetic rat.

Abstract

In the rat the assumption of a primary effect of moderate doses of biguanides on intestinal absorption is supported by the following results: 1. The tolerance to parenteral glucose administration was not improved. — 2. Afteroral pretreatment the hyperglycaemia induced byoral glucose was decreased. — 3. After pretreatmentin vivo the transport of glucose through the intestinal wall was inhibited. — 4. The intestinal glucose transport was inhibited alsoin vitro in the presence of biguanides at concentrations to be expected in intestinal tissuein vivo after efficient doses. — 5. In the streptozoocin-diabetic rat there was a strong correlation between the feeding state and the hypoglycaemie effect of biguanides. In streptozotocin-diabetic rats previously starved and then refed, the hypoglycaemie effect decreased with decreasing doses of the diabetogenic agent. — 6. The relative potency of various biguanides was similar with regard to their effects on hyperglycaemia and on the intestinal glucose transport. — The results suggest, however, that in the rat further events, probably triggered by the inhibition of intestinal absorption, are involved in the mechanism of action of biguanides.