HYPOTHALAMIC CHOLINERGIC ACTIVITY ASSOCIATED WITH 2-DEOXYGLUCOSE-INDUCED HYPERGLYCEMIA

In order to clarify the role of the hypothalamic cholinergic system in the regulation of peripheral glucose metabolism, we investigated hypo thalamic cholinergic activity after administration of 2-deoxyglucose ( 2-DG). Intravenous administration of 2-DG (500 mg/kg) caused marked hy perglycemia; the level of plasma glucose increased by 2.1 times over t he initial levels at 20 min. For evaluation of the cholinergic activit y, we analyzed extracellular levels of acetylcholine (ACh) and choline using brain microdialysis, as well as measuring their tissue levels i n the ventromedial hypothalamic nucleus (VMH) and lateral hypothalamus (LH) of rats killed by microwave. In the microdialysis perfusate, ext racellular levels of ACh and the metabolite choline were increased by 2-DG administration. In the tissue, a dose dependent decrease in the A Ch content and a corresponding increase in the choline content were ob served in both hypothalamic nuclei 20 min after administration of 2-DG . These data show that cholinergic activity is increased after 2-DG ad ministration. Both the plasma glucose increment and the fluctuation of ACh and choline content were reduced in pentobarbital anesthetized ra ts. In 6-hydroxydopamine (6-OHDA) pretreated rats, the hypothalamic co ntent of norepinephrine (NE) was reduced to one-third of that in contr ols, but there was no significant effect on the hyperglycemia or incre ase in hypothalamic tissue choline levels following 2-DG. Our results sus est the involvement of the hypothalamic cholinergic system in 2-DG -induced hyperglycemia.