Beverly J L, Martin R J
Department of Physiological Sciences and Food Intake Laboratory, University of California, Davis 95616.
Am J Physiol. 1990 Mar;258(3 Pt 2):R697-703. doi: 10.1152/ajpregu.1990.258.3.R697.
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.
在参与血糖调节的几个脑区中,测量了γ-氨基丁酸合成的限速酶谷氨酸脱羧酶(GAD)的活性变化对胰岛素诱导的低血糖的反应。注射胰岛素30分钟后,测得大鼠腹内侧核(VMN)中GAD活性增加了20%。这种增加与血清葡萄糖的降低(r = -0.74)和食物摄入量的增加(r = 0.44)显著相关。胰岛素注射后5至30分钟内,VMN中GAD活性的增加呈线性,且与血清葡萄糖的下降同时发生。用50%葡萄糖溶液进行胃预负荷预处理可减轻血清葡萄糖的下降、食物摄入量的增加以及GAD活性的增加。嘌呤霉素抑制蛋白质合成并未阻止葡萄糖的下降,但未观察到VMN中GAD活性的增加或对胰岛素反应的食物摄入量的增加。如果大鼠禁食,胰岛素注射6小时后VMN中GAD活性也会增加。除VMN外,在任何脑区均未测得GAD活性的一致变化。这些试验结果表明,VMN中GAD活性的增加与血清葡萄糖的降低有关,可能参与了与胰岛素给药相关的进食增加。