The inhibitory action of buformin, a biguanide on gluconeogenesis from alanine and its transport system in rat livers.
The effect of buformin, a biguanide, on gluconeogenesis from 10 mM alanine in the presence of 143 nM glucagon were studied using isolated rat liver perfusions. In addition, to investigate possible mechanisms of biguanide action, alanine utilization in isolated rat liver perfusion and [3H]alanine uptake in isolated hepatocytes were observed. Buformin (1.85 mM) strongly inhibited gluconeogenesis from alanine in the presence of glucagon in both normal and streptozocin-induced diabetic rat livers. This inhibition was followed by a decrease in alanine utilization. Both of these inhibitory effects of buformin were dose-dependent. [3H]Alanine uptake was significantly inhibited by buformin. The effect of this agent was similar to but weaker than that of ouabain. However, tolbutamide failed to reduce either alanine utilization or [3H]alanine uptake, although this drug significantly inhibited gluconeogenesis from alanine. These data suggest that biguanides may reduce hepatic alanine utilization via the inhibition of Na+/L-alanine transport activity as one possible mechanism, resulting the inhibition of gluconeogenesis from alanine in the presence of glucagon.
Hotta
N
N
Third Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Komori
T
T
Kobayashi
M
M
Sakakibara
F
F
Koh
N
N
Sakamoto
N
N
D020155:3-Hydroxybutyric Acid; D000090:Acetoacetates / Q000378:metabolism; D000409:Alanine / Q000187:drug effects / Q000493:pharmacokinetics*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002026:Buformin / Q000494:pharmacology*; D002469:Cell Separation; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D005934:Glucagon / Q000494:pharmacology; D005943:Gluconeogenesis / Q000187:drug effects*; D006885:Hydroxybutyrates / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010477:Perfusion; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D051381:Rats; D017208:Rats, Wistar; D014044:Tolbutamide / Q000494:pharmacology
D000090:Acetoacetates; D006885:Hydroxybutyrates; D007773:Lactates; D011773:Pyruvates; D019344:Lactic Acid; C016635:acetoacetic acid; D019289:Pyruvic Acid; D005934:Glucagon; D014044:Tolbutamide; D000409:Alanine; D020155:3-Hydroxybutyric Acid; D002026:Buformin