Influence of serum glucose on glutamate decarboxylase activity in the ventromedial nucleus of rats

Abstract

Changes in the activity of glutamate decarboxylase (GAD), the rate-limiting enzyme in gamma-aminobutyric acid synthesis, in response to insulin-induced hypoglycemia were measured in several brain areas involved in glucoregulation. A 20% increase in GAD activity in the ventromedial nucleus (VMN) of rats was measured 30 min after injections of insulin. The increase was significantly correlated with the decrease in serum glucose (r = -0.74) and increased food intake (r = 0.44). The increase in VMN GAD activity was linear between 5 and 30 min after insulin injection and coincided with the decline in serum glucose. Pretreatment with a gastric preload of a 50% glucose solution attenuated the decline in serum glucose, the increase in food intake, and the increase in GAD activity. Inhibition of protein synthesis by puromycin did not block the decrease in glucose, but neither the increase in GAD activity in the VMN nor the increase in food intake in response to insulin was observed. The increase in VMN GAD activity also was present 6 h after insulin injection if rats were denied access to food. No consistent changes in GAD activity were measured in any brain area other than the VMN. The results of these trials suggest that the increase in VMN GAD activity is associated with the decrease in serum glucose and may be involved in the increased feeding associated with insulin administration.