Effects of buformin on the metabolism of the isolated haemoglobin-free perfused hindlimb of normal rats

Abstract

Summary. Using the isolated, haemoglobin-free, perfused resting hindlimb of normal rats buformin neither had a direct insulin-like effect on glucose uptake by muscle tissue nor potentiated the effect of insulin on glucose uptake after oral pretreatment for one or several days with low and high doses (30 mg--350 mg/kg). Effects on glycogenolysis could not be detected. Glycerol release was inhibited after several days of pretreatment with low and high doses of buformin. The utilization of added oleate was also partly inhibited. The level of energy rich phosphates in the muscle tissue and oxygen consumption were not affected under any of the conditions used in these experiments.Key words: Buformin, muscle metabolism, isolated perfused hindlimb of the rat.The mode of action of the biguanides is still under discussion. In recent studies from this laboratory concerning the effect of buformin on muscle metabolism we observed an increased glycogen content and a high rate of radioglucose incorporation into the glycogen of the diaphragm of normal rats in vivo after a long term oral administration of buformin --150--175 mg/kg -- [12]. Similar results were reported with the perfused rat heart [15] and in in vivo experiments [11]. In order to investigate a direct action of buformin on glucose utilization in skeletal muscle, the isolated perfused hindlimb of the rat was used as a suitable model for metabolic studies [13,14]. In this study we report the effect of low and high doses of buformin, administered orally for one or several days, on the metabolism of the perfused resting hindlimb of normal rats.

A perfused ruminant muscle preparation

“…Corresponding with the decline in muscle glycogen was a relatively large production of lactate (see Fig. 4) by the perfused sheep hemidiaphragm (729/tmol/h/ 30 g for the standard perfusion medium) which was greater than that reported for the perfused rat hind-limb, for example, 180 ± 54 (7) /tmol/h/30 g muscle (Ruderman et al 1971), 207 ± 12-5 (15) /tmol/h/30 g muscle (Reimer et al 1975) and 249 ± 21 (12) /tmol/h/30 g muscle (Strohfeldt et al 1975a); it was, however, similar to that produced by the perfused rat diaphragm (559/tmol/h/30 g muscle (Hollanders, 1968) and 679/tmol/h/30 g muscle (Rowlands, 1969); both values are minimum values over the perfusion period). The ratio of lactate/pyruvate produced by the perfused muscle (approximately 95, see Figs 3 and 4) was high compared with values obtained for the perfused rat hind-limb, for example, 28-5 (Strohfeldt, Kettl & Weinges, 1974) and 10-9 (Strohfeldt et al 19756), possibly indicating a relatively reduced state of the perfused sheep hemidiaphragm.…”