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 hypothalamic cholinergic activity after administration of 2-deoxyglucose (2-DG). Intravenous administration of 2-DG (500 mg/kg) caused marked hyperglycemia; the level of plasma glucose increased by 2.1 times over the initial levels at 20 min. For evaluation of the cholinergic activity, we analyzed extracellular levels of acetylcholine (ACh) and choline using brain microdialysis, as well as measuring their tissue levels in the ventromedial hypothalamic nucleus (VMH) and lateral hypothalamus (LH) of rats killed by microwave. In the microdialysis perfusate, extracellular levels of ACh and the metabolite choline were increased by 2-DG administration. In the tissue, a dose dependent decrease in the ACh content and a corresponding increase in the choline content were observed in both hypothalamic nuclei 20 min after administration of 2-DG. These data show that cholinergic activity is increased after 2-DG administration. Both the plasma glucose increment and the fluctuation of ACh and choline content were reduced in pentobarbital anesthetized rats. In 6-hydroxydopamine (6-OHDA) pretreated rats, the hypothalamic content of norepinephrine (NE) was reduced to one-third of that in controls, but there was no significant effect on the hyperglycemia or increase in hypothalamic tissue choline levels following 2-DG. Our results suggest the involvement of the hypothalamic cholinergic system in 2-DC-induced hyperglycemia.