Isoflavone-genistein changes tissue glycogen and blood glucose concentration in ovariectomized rats: possible ways of action

The effects of genistein, a naturally occurring plant isoflavone, on carboh ydrate metabolism of ovariectomized rats were studied. On the basis of resu lts obtained previously, the trial was undertaken to explain the possible m echanisms responsible for observed changes. Two types of experiments were c arried our: (i) two groups of ovariectomized rats were fed for 14 days with diets supplemented with 0.01% or 0.1% of genistein and (ii) the direct eff ect of genistein on liver metabolism was examined by mean of liver perfusio n; isoflavone was added to the perfusion medium in the amount of 300 mu mol /l. Genistein feeding led to a statistically significant increase of blood gluc ose level and a decrease in the liver and muscle glycogen concentration. Th ese effects could result from an alteration in the secretion of pancreatic hormones. The glucagon blood level was enhanced and insulin concentration d iminished after genistein treatment. Also, the liver glucagon receptor sens itivity increased due to genistein action as measured by the change in the dissociation constant of these receptors. The genisien-supplemented diet di d not significantly alter the characteristics of the insulin receptors. All these changes were observed only in rats treated with the higher dose (0.1 %) of genistein. The effects of feeding the lower dose (0.01%) of isoflavon e were negligible. In the liver perfusion, a direct effect of the high dose of genistein (300 mu mol/l of medium) on carbohydrate metabolism was shown. It manifested its elf in the reduction of the liver glycogen measured after perfusion and, ma inly, in the retention of free glucose in the liver and a decrease of its o utput into the perfusate. On the basis of the results presented, it is concluded that: (i) the influe nce of genistein on carbohydrate metabolism of ovariectomized rats may be m ediated by pancreatic hormones and (ii) impaired glucose exchange in the li ver and probably also in the skeletal muscle can be attributed directly to genistein.