Mechanism of intrahippocampal neostigmine-induced hyperglycemia in fed rats.
We previously reported that the injection of neostigmine, an acetylcholine esterase inhibitor, into the dorsal hippocampus produced hepatic venous plasma hyperglycemia associated with an increase of epinephrine and glucagon in anesthetized fed rats. To evaluate the relative contribution of these glucoregulatory hormones and the nervous system to the net hyperglycemic response, we unilaterally injected neostigmine (5 x 10(-8) mol) into the dorsal hippocampus in the following groups of rats: intact rats with bilateral adrenalectomy to eliminate the action of epinephrine, and rats receiving a constant infusion of somatostatin and insulin to prevent the glucagon response and to maintain the basal insulin level. Hepatic venous plasma levels of glucose, immunoreactive glucagon, immunoreactive insulin, epinephrine, and norepinephrine were determined. The area under the glucose curve during the 120-min period following the injection of neostigmine was compared between groups. The areas under the glucose curve for rats receiving somatostatin and insulin, adrenalectomy rats, and adrenalectomy rats receiving somatostatin and insulin were, respectively, 82, 31, and 61% of that for intact rats. The fashion of hippocampal stimulated hyperglycemia with neostigmine was similar to that after injection of neostigmine into the third cerebral ventricle. 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.
Iguchi
A
A
Third Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Uemura
K
K
Miura
H
H
Ishiguro
T
T
Nonogaki
K
K
Tamagawa
T
T
Goshima
K
K
Sakamoto
N
N
D000818:Animals; D004837:Epinephrine / Q000502:physiology*; D005934:Glucagon / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D006943:Hyperglycemia / Q000139:chemically induced / Q000503:physiopathology*; D007033:Hypothalamus, Middle / Q000502:physiology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D009388:Neostigmine; D009638:Norepinephrine / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains
D007328:Insulin; D009388:Neostigmine; D005934:Glucagon; D009638:Norepinephrine; D004837:Epinephrine