Abstract

5-Methylpyrazole-3-carboxylic acid in concentrations between 10^-8 and 10^-6 M inhibited the glycerol release of adipose tissue of fasted-refed rats. Insulin and 5-methylpyrazole-3-carboxylic acid partially prevented the loss of glycogen even in the absence of any substrate in the medium. Maximal glycogen turnover in vitro in the presence of glucose, fructose, and insulin amounted to 5 µmoles of hexose per gram per hour. 5-Methylpyrazole-3-carboxylic acid stimulated the incorporation of fructose-U-¹⁴C into glycogen out of proportion to its effects on overall fructose metabolism. This effect was counteracted by insulin but not by phlorizin. Insulin doubled fructose uptake of adipose tissue of fasted-refed rats but did not stimulate the incorporation of fructose-U-¹⁴C into glycogen. It stimulated the incorporation of glucose-U-¹⁴C into glycogen only at high rates of glucose uptake. These results support the concept that insulin and 5-methylpyrazole-3-carboxylic acid inhibit phosphorylase and increase glycogen synthetase activity. The difference between the activity of these two substances could best be explained by the existence of different pools of glucose 6-phosphate.