Insulinotrophic Drugs: Effect on Intestinal Absorption of Sugar

Abstract

The effect of some insulinotrophic drugs on the transport of sugar was investigated in fasted, narcotized rats by continuous perfusion of cannulated long intestinal loops with galactose solution (18 mM.) circulated by air lift. Three consecutive perfusions (fifty minutes each) were performed in each rat, the drug being given in the second perfusion only. The rate of galactose disappearance was expressed as per cent of that in the first perfusion in the same rat.Tolbutamide (50 mg./l kg. weight), glycodiazine (50 mg./l kg. weight), glisoxepid (BAY 4231, 2 mg./l kg. weight) and glibenclamide (0.25 mg./l kg. weight) were found to increase the rate of galactose disappearance in the second perfusion by 21 per cent, 5 per cent, 12 per cent and 25 per cent, respectively, and in the third perfusion by 21 per cent, 26 per cent, 32 per cent and 21 per cent, respectively, as compared to the rate in the corresponding perfusion of a control group. This increase was significant (P values < 0.05) with all drugs in the second and third perfusions with the exception of glisoxepid in the second perfusion. These results are discussed in relation to the action of insulin and the effect of diabetes on intestinal absorption of sugars. DIABETES 23: 112-16, February, 1974. In a previous work, 1 we showed that metformin, an oral hypoglycemic agent of the biguanide group, markedly inhibited the transport of glucose by everted sacs of guinea pig intestine. In a later report, Kruger et al. , 2 using the same technic in rats, demonstrated a similar effect with phenformin.It seemed of interest to investigate the effect of the other group of oral hypoglycemics on the transport of sugar by the intestine. To the best of our knowledge, there were no reports in the literature concerning this point. The drugs selected for the present study were: tolbutamide (Rastinon), glycodiazine (Lycanol), glisoxepid (BAY 4231) and glibenclamide (Daonil).The present paper describes the effect of these insulinotrophic drugs on the transport of sugar by long intestinal loops continuously perfused in situ.