3-mercaptopicolinic acid, an inhibitor of gluconeogenesis.
1. 3-Mercaptopicolinic acid (SK&F 34288) inhibited gluconeogenesis in vitro, with lactate as substrate, in rat kidney-cortex and liver slices. 2. In perfused rat livers, gluconeogenesis was inhibited when lactate, pyruvate or alanine served as substrate, but not with fructose, suggesting pyruvate carboxylase or phosphoenolpyruvate carboxylase as the site of inhibition. No significant effects were evident in O(2) consumption, hepatic glycogen, urea production, or [lactate]/[pyruvate] ratios. 3. A hypoglycaemic effect was evident in vivo in starved and alloxan-diabetic rats, starved guinea pigs and starved mice, but not in 4h-post-absorptive rats. 4. In the starved rat the hypoglycaemia was accompanied by an increase in blood lactate. 5. A trace dose of [(14)C]lactate in vivo was initially oxidized to a lesser extent in inhibitor-treated rats, but during 90min the total CO(2) evolved was slightly greater. The total amount of the tracer oxidized was not significantly different from that in the controls.
D000085:Acetates / Q000378:metabolism; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D002250:Carbon Radioisotopes; D003864:Depression, Chemical; D003921:Diabetes Mellitus, Experimental; D005943:Gluconeogenesis / Q000187:drug effects*; D006168:Guinea Pigs; D007003:Hypoglycemia; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D051379:Mice; D010101:Oxygen Consumption; D010477:Perfusion; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000037:antagonists & inhibitors; D010848:Picolinic Acids / Q000494:pharmacology*; D011766:Pyruvate Carboxylase / Q000037:antagonists & inhibitors; D011773:Pyruvates / Q000378:metabolism; D051381:Rats; D013217:Starvation; D013438:Sulfhydryl Compounds / Q000494:pharmacology*
D000085:Acetates; D002250:Carbon Radioisotopes; D007773:Lactates; D008112:Liver Glycogen; D010848:Picolinic Acids; D011773:Pyruvates; D013438:Sulfhydryl Compounds; D002245:Carbon Dioxide; C008363:3-mercaptopicolinic acid; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D011766:Pyruvate Carboxylase