Changes in plasma amino acids levels and in vivo gluconeogenesis from alanine in rats chronically treated with sulfonylureas.

Abstract

Female rats were treated with two daily equihypoglycemic doses (as observed in acute treatment) of tolbutamide, glibenclamide or glipentide . by stomach tube, and were compared with control ammals treated with the suspending medium alone. On day 29 the rats were subjected to a 48 h fast and then were injected intraperitoneally with 100 .μMoles of C' -alanine. Blood samples were collected before and 5, 15 and 30 minutes after the alanine injection, at which time the animals were killed. Blood glucose levels increased after the injection of alanine in all groups, but at the different times stll:died, both the glibenclamide and glipentide treated_ anu_n~ls showed hypoglycemia versus controls. The rad10act1:"1ty found in blood glucose and liver glycogen and glycendeglycerol decreased in the glibenclamide treated anima~s compared with controls while in the other groups 1t was similar. The increase in liver glycogen after the injection of alanine was also diminished in the_ glibenclamide treated animals. Alanine produced an mcrease in the plasma levels of gluconeogenic, basic, aromatic and sulphur-containing amino acids in the controls, while in the animals treated with glipentide the alanine effect was less pronounced. The results show an impairment of gluconeogenic function in glibenclamide treated animals. The effects of both tolbutamide and glipentide were less dramatic. Nevertheless, the findings hinted at an effect of both drugs upon glycogen metabolism in liver.