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The present studies were undertaken to investigate the possible mechanism(s) of action of 2,2-dimethyl-1-(4-methylphenyl)-1-propanone (SaH 50-283) on food efficiency in rats. SaH 50-283, unlike phenformin (DBI), did not inhibit glucose absorption. However, hyperglycemia induced by oral maltose, lactose or starch load was markedly inhibited in animals pretreated with SaH 50-283. The ED25 for lowering blood sugar levels following an oral maltose load was calculated to be 12 mg/kg. SaH 50-283 could be administered as long as 7 hr prior to a maltose load and still maintain its effect. Food efficiency was significantly (P less than .01) lowered in rats pretreated with SaH 50-283 1 hr prior to a 2 hr feeding period of a purified high carbohydrate diet. It was concluded that the lowering of maltase activity in the brush border of animals treated with SaH 50-283 could partially account for its mechanism of action in lowering food efficiency in rats.

Acarbose, an alpha-glycosidehydrolase inhibitor, reduced hyperglycemia after an oral sucrose or starch load in the rat. The compound showed weaker activity in inhibiting maltose-induced hyperglycemia and no effect on glucose or lactose tolerance in the rat. In the Cebus monkey, the oral starch tolerance curve was significantly inhibited by acarbose at a dose comparable to that showing activity in man. Therefore, the Cebus monkey appears to be a suitable animal model for studying agents which affect starch tolerance in man.

The present studies were undertaken to define the effects of 3-phenylpropylaminoguanidine-HCl (SaH 43-522 or 43-522) on glucose active transport in the gastrointestinal tract. A comparison with phenformin (DBI) was made in certain studies. SaH 43-522 is 2 to 3 times more potent than DBI with regard to its inhibitory effect on glucose active transport in the gastrointestinal tract of rats. The activity lasts for 5 hr after oral administration. SaH 43-522 also inhibits intestinal glucose absorption in the hamster, guinea-pig, dog, and monkey in either in vitro or in vivo systems. SaH 43-522 differs from DBI in that when glucose active transport is studied in vitro by adding drug into the incubation fluid, DBI is active only when the drug is present in the incubation fluids on both the mucosal and serosal sides, whereas SaH 43-522 is active in inhibiting intestinal glucose active transport when the drug is present in mucosal fluid only.