Involvement of the Hippocampus in Central Nervous System-Mediated Glucoregulation in Rats

Abstract

To find out whether the hippocampus is involved in central nervous system-mediated glucoregulation, we injected saline, neostigmine, dopamine, norepinephrine, bombesin, beta-endorphin, somatostatin, and prostaglandin F2 alpha into the dorsal hippocampus in anesthetized fed rats. After injection of dopamine, norepinephrine, bombesin, beta-endorphin, somatostatin, or prostaglandin F2 alpha, the level of hepatic venous plasma glucose did not differ from that in saline-treated control rats. However, neostigmine, an inhibitor of acetylcholine esterase, caused a dose-dependent increase in the hepatic venous plasma glucose concentration. This neostigmine-induced hyperglycemia was dose-dependently suppressed by coadministration of atropine, but not by hexamethonium. Injection of neostigmine (5 X 10(-8) mol) resulted in an increase not only in glucose but also in glucagon, epinephrine, and norepinephrine in hepatic venous plasma. In bilateral adrenalectomized rats, neostigmine-induced hyperglycemia was suppressed, but the hepatic venous plasma glucose concentration still increased significantly. These results indicate that the hippocampus is involved in central nervous system-mediated glucoregulation through cholinergic muscarinic activation, partly via epinephrine secretion.

Mechanism of Intrahippocampal Neostigmine-lnduced Hyperglycemia in Fed Rats

“…We have previously reported that the hippocampus was involved in CNS-mediated glucoregulation through cholinergic muscarinic activation [1], based on the fact that microinjection of neostigmine into the dorsal hippo campus leads to hepatic venous hyperglycemia associated with increased levels of glucagon, epinephrine, and nor-47 Table 3. Hepatic venous plasma epinephrine (pg/ml) and norepinephrine (pg/ml) concentrations following microinjection of saline alone 0.2 pi or saline with 5 x 10~8 mol neostigmine into the hippocampus…”

“…Forty-five minutes later, rats were placed on a stereotaxic appa ratus, and 0.2 pi of saline with or without neostigmine (5 x I O'8 mol, Sigma Chemical Co., St. Louis, Mo.) was injected unilaterally into the dorsal hippocampus, as previously described [1],…”

“…However, the periph nephrine, norepinephrine, and glucagon and the sup pression of insulin secretion in intact rats [1], In the present study, to evaluate the relative roles of these glucoregulatory hormones and the nervous system in the hyperglycemic response to hippocampal stimulation by neostigmine, we used ADX rats to eliminate the action of epinephrine and intact or ADX rats given a somatostatin infusion to suppress the glucagon response to neostig mine. We then determined the relative contribution of each glucoregulatory factor to the net hyperglycemic re sponse.…”

“…Therefore, we investigated hyperglycemia in rats with lesions of ventromedial hypothalamus and found that the response to hippocampal neostigmine was significantly inhibited by the hypothalamic lesion. These findings suggest that the glucoregulatory hippocampal activity evoked by neostigmine may be transmitted to peripheral organs via the ventromedial hypothalamus.We have previously reported that injection of neostig mine, an acetylcholine esterase inhibitor, into dorsal hip pocampus produces hepatic venous hyperglycemia in anesthetized fed rats via cholinergic muscarinic activa tion, and that bilateral adrenalectomy reduced the extent of this hyperglycemic response [1]. However, the periph Received: December 27, 1990 Accepted alter revision: May 14.…”

“…However, the periph Received: December 27, 1990 Accepted alter revision: May 14. 1991 eral pathways transmitting the hippocampal activity evoked by neostigmine have not been fully determined since the hyperglycemic response was only partially in hibited in adrenalectomized (ADX) rats, [1].Hippocampally induced hyperglycemia was accompa nied by an increase in the hepatic venous levels of epiDr. Akihisa Iguchi…”