355 Horm. Metab. Res. 7 (1975) 355
© Georg Thieme Verlag Stuttgart Immediate Effects of Buformin on Muscle Metabolism*
P. Strohfeldt, H. Kettl, U. Obermaier and K.F. Weinges
The mode of action of the biguanides is still under discussion. We recently reported our results, concerning the effect of buformin on the metabolism of the isolated hemoglobin-free perfused hindlimb of normal rats, after several days of oral pretreatment (Stroh/eldt, Kettl, Obennaier and Weinges 1975). In order to have known concentrations of the drug in the system, the effects on the metabolism of the perfused hindlimb of buformin are reported after addition to the medium. 24 hour fasting male Sprague-Dawley rats (160-240 gm) were used. Buformin (kindly supplied by the Chemie Griinenthal, GmbH, Stolberg/Rhld., Germany) was added to the medium at a range from 1 to 1000 I'g/ml. The perfusion lasted for 1 hour. The perfusion technique, apparatus, synthetic medium and used analytical methods have been reported elsewhere (Strohfeldt 1973, Stroh/eldt, Kettl and Weinges 1974). No change at a11 could be observed in the metabolic performance of the muscle tissue up to 100 J.Ig/ml buformin. At 1000 J.Ig/ml the glucose uptake was unaffected, the lactate production increased twofold accounting for a11 the glucose taken up; there was a significant rem oval of pyruvate from the medium with an increase of the Iactate/pyruvate ratio but without significant glycogenolysis; the oxygen consumption decreased without affecting the level of energy-rich phosphates (s. Table). In contrast to the findings of most authors working with the incubated diaphragm of rats or guinea pigs (s. review by Beckmann 1971), buformin was uncapable to increase the glucose uptake of the perfused hindlimb although we partly used concentrations of the drug far above those measured in the plasma of patients « 1 J.Ig/ml; Lintz, Berger, Aenishaenslin, Kutova, Baerlocher, Kapp and Beckmann 1974). Similar observations are known from other perfusion models (Williamson, Walker and Renold 1963, Butterfield 1968). Our results support the hypo thesis of Williamson, Walker and Renold (1963). It remains, however, yet to be clarified why an increased state of reduction of the mitochondrial pyridine nucleotides is not associated with an increased glucose uptake of the tissue. Table. Metabolism of the isolated perfused hindlimb of normal rats under the influence of added buformin. Values are expressed as X±SX, • = significantly different from control (p
© Georg Thieme Verlag Stuttgart Immediate Effects of Buformin on Muscle Metabolism*
P. Strohfeldt, H. Kettl, U. Obermaier and K.F. Weinges
The mode of action of the biguanides is still under discussion. We recently reported our results, concerning the effect of buformin on the metabolism of the isolated hemoglobin-free perfused hindlimb of normal rats, after several days of oral pretreatment (Stroh/eldt, Kettl, Obennaier and Weinges 1975). In order to have known concentrations of the drug in the system, the effects on the metabolism of the perfused hindlimb of buformin are reported after addition to the medium. 24 hour fasting male Sprague-Dawley rats (160-240 gm) were used. Buformin (kindly supplied by the Chemie Griinenthal, GmbH, Stolberg/Rhld., Germany) was added to the medium at a range from 1 to 1000 I'g/ml. The perfusion lasted for 1 hour. The perfusion technique, apparatus, synthetic medium and used analytical methods have been reported elsewhere (Strohfeldt 1973, Stroh/eldt, Kettl and Weinges 1974). No change at a11 could be observed in the metabolic performance of the muscle tissue up to 100 J.Ig/ml buformin. At 1000 J.Ig/ml the glucose uptake was unaffected, the lactate production increased twofold accounting for a11 the glucose taken up; there was a significant rem oval of pyruvate from the medium with an increase of the Iactate/pyruvate ratio but without significant glycogenolysis; the oxygen consumption decreased without affecting the level of energy-rich phosphates (s. Table). In contrast to the findings of most authors working with the incubated diaphragm of rats or guinea pigs (s. review by Beckmann 1971), buformin was uncapable to increase the glucose uptake of the perfused hindlimb although we partly used concentrations of the drug far above those measured in the plasma of patients « 1 J.Ig/ml; Lintz, Berger, Aenishaenslin, Kutova, Baerlocher, Kapp and Beckmann 1974). Similar observations are known from other perfusion models (Williamson, Walker and Renold 1963, Butterfield 1968). Our results support the hypo thesis of Williamson, Walker and Renold (1963). It remains, however, yet to be clarified why an increased state of reduction of the mitochondrial pyridine nucleotides is not associated with an increased glucose uptake of the tissue. Table. Metabolism of the isolated perfused hindlimb of normal rats under the influence of added buformin. Values are expressed as X±SX, • = significantly different from control (p
