HYPOTHALAMIC CHOLINERGIC ACTIVITY AND 2-DEOXYGLUCOSE-INDUCED HYPERGLYCEMIA

To clarify the role of the hypothalamic cholinergic system in the regu lation of peripheral glucose metabolism, we investigated hypothalamic cholinergic activities after administration of a-deoxyglucose (2-DG). Intravenous administration of 2-DG (500 mg/kg) caused neuroglycopenia and marked hyperglycemia; the level of plasma glucose increased to 210 % of the initial levels at 20 min. For evaluation of the cholinergic a ctivity, we employed a microwave device and subsequently analyzed the contents of acetylcholine (ACh) and choline after microdissection of t he hypothalamic nuclei, ventromedial hypothalamic nucleus (VMH), later al hypothalamus (LH), and paraventricular nucleus (PVN). In addition, we analyzed fluctuation of extracellular levels of ACh using in vivo b rain microdialysis. A decrease in the ACh content, and a corresponding increase in the choline content, was observed in those hypothalamic n uclei 20 min after administration of 2-DG. In the microdialysis perfus ate, on the other hand, extracellular level of ACh was increased by 2- DG administration. These data show that ACh release, which is choliner gic activity, was increased after 2-DG administration. Our results sug gest the involvement and importance of the hypothalamic cholinergic sy stem in 2-DG-induced hyperglycemia. (C) 1997 Elsevier Science Inc.