1. Phenethylbiguanide inhibits the synthesis of phosphoenolpyruvate from malate or 2-oxoglutarate by isolated guinea-pig liver mitochondria. This inhibition is time- and concentration-dependent, with the maximum decrease in the rate of phosphoenolpyruvate synthesis (80%) evident after 10min of incubation with 1mm-phenethylbiguanide. 2. The phosphorylation of ADP by these mitochondria is also inhibited at increasing concentrations of phenethylbiguanide and there is a progressive increase in AMP formation. Guinea-pig liver mitochondria are more sensitive to this inhibition in oxidative phosphorylation caused by phenethylbiguanide than are rat liver mitochondria. 3. Simultaneous measurements of O2 consumption and ADP phosphorylation with guinea-pig liver mitochondria oxidizing malate plus glutamate in State 3 indicated that phenethylbiguanide at low concentrations (0.1mm) inhibits respiration at Site 1. At higher phenethylbiguanide concentrations Site 2 is also inhibited. 4. Gluconeogenesis from lactate, pyruvate, alanine and glycerol by isolated perfused guinea-pig liver is inhibited to various degrees by phenethylbiguanide. Alanine is the most sensitive to inhibition (60% inhibition of the maximum rate by 0.1mm-phenethylbiguanide), whereas glycerol is relatively insensitive (25% inhibition at 4mm). 5. Gluconeogenesis from lactate and pyruvate by perfused rat liver was also inhibited by phenethylbiguanide, but only at high concentrations (8mm). Unlike guinea-pig liver, the inhibitory effect of phenethylbiguanide on rat liver was reversible after the termination of phenethylbiguanide infusion. 6. The time-course of inhibition of gluconeogenesis from the various substrates used in this study indicated a time-dependency which was related in part to the concentration of infused phenethylbiguanidine. This time-course closely paralleled that noted for the inhibition by phenethylbiguanide of phosphoenolpyruvate synthesis in isolated guinea-pig liver mitochondria.
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October 1974
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Research Article|
October 01 1974
Phenethylbiguanide and the inhibition of hepatic gluconeogenesis in the guinea pig
Korechika Ogata;
Korechika Ogata
1Fels Research Institute and Department of Biochemistry, Temple University Medical School, Philadelphia, Pa. 19140, U.S.A.
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Mireille Jomain-Baum;
Mireille Jomain-Baum
1Fels Research Institute and Department of Biochemistry, Temple University Medical School, Philadelphia, Pa. 19140, U.S.A.
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Richard W. Hanson
Richard W. Hanson
1Fels Research Institute and Department of Biochemistry, Temple University Medical School, Philadelphia, Pa. 19140, U.S.A.
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Publisher: Portland Press Ltd
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 1974 The Biochemical Society
1974
Biochem J (1974) 144 (1): 49–57.
Citation
Korechika Ogata, Mireille Jomain-Baum, Richard W. Hanson; Phenethylbiguanide and the inhibition of hepatic gluconeogenesis in the guinea pig. Biochem J 1 October 1974; 144 (1): 49–57. doi: https://doi.org/10.1042/bj1440049
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