Studies of the action of hypoglycin-A, an hypoglycaemic substance

Some biological effects of hypoglycin-A, a compound isolated from the fruit of Blighia sapida, have been investigated. Administration of this compound to animals caused drowsiness progressing to coma, and when large doses were given the animals died. For the rat, the oral and intraperitoneal LD50 values were 98 and 97 mg./kg. respectively. Fasting increased the toxicity considerably. The most outstanding biochemical change produced by hypoglycin-A was a delayed hypoglycaemia, the depth of which was related to the dose. The hypoglycaemia was preceded by exhaustion of liver glycogen. There were also smaller decreases in the glycogen stores of the heart, skeletal muscle and kidney, without any increase in blood pyruvate or lactate. Hypoglycin-A lessened the effect of adrenaline on blood glucose and decreased both glucose tolerance and insulin sensitivity. Hypoglycin-A also decreased the oxygen consumption and carbon dioxide production of the intact rat. All these effects are consistent with the hypothesis that the primary action of hypoglycin-A is the interference with glycogen production by the liver.