Effects of Biguanides on Gluconeogenesis in Rats and Guinea Pigs

In guinea pigs doses of 10 mg/kg lower blood-glucose. In rabbits and rats no effect or only at very high doses could be demonstrated. Soling has already shown in guinea pigs that the fall in blood-glucose is accompanied by an increase in blood-lactate. Our own experiments demonstrated that 10 mg/kg Phenformin (i.p.) in guinea pigs caused a nearly statistical significant fall in blood-glucose and a diminished concentration of liver-glycogen. The increase of lactate at this dose is in contrast highly significant. In our experiments with isolated kidney and liver cells the effects of pretreatment with Phenformin on gluconeogenesis and pyruvate-consumption in normal rats, alloxandiabetic rats and guinea pigs were studied (Fig. 1a and 1b). In normal rats, no influence of Phenformin on glucose-formation could be seen. In contrast to this a strong inhibition of gluconeogenesis could be demonstrated in the tissue of guinea pigs (Fig. 1b). There are also differences in liver and kidneys in pretreated alloxan-diabetic rats; the glucose-formation rate is higher than in normal animals. The effects observed in the guinea pigs could be related to the compartmentation of the gluconeogenetic key enzymes which differs from that of the rat.