Mechanism responsible for the hypoglycemic actions of dichloroacetate and 2-chloropropionate.

摘要: Abstract Dichloroacetate, an activator of the pyruvate dehydrogenase complex, is known to lower blood glucose, lactate, pyruvate, and alanine when given diabetic 24 h fasted rats. Under certain conditions, especially carboxylase made rate limiting for want bicarbonate, dichloroacetate effectively inhibits glucose synthesis from lactate by isolated hepatocytes. 2-Chloropropionate also activates lowers in rats, but stimulates gluconeogenesis or Dichloroacetate catabolized glyoxylate thence oxalate liver cells, whereas 2-chloropropionate cannot be these products. Glyoxylate are potent inhibitors alanine, not dihydroxyacetone. Inhibition much more pronounced a bicarbonate-deficient medium, which probably gluconeogenesis. It seems likely, therefore, that inhibition actually caused oxalate, carboxylation. Nevertheless, major effect dichloroacetate, sole 2-chloropropionate, on concentration limit substrate availability hepatic Since oxalic acid stone formation renal dysfunction may prove side effects any therapeutic application we suggest further studies treatment hyperglycemia lactic acidosis with activators carried out rather than dichloroacetate.