Mechanism of central hyperglycemic effect of cholinergic agonists in fasted rats

Abstract

The influence of cholinergic agonists on central nervous system (CNS) regulation of blood sugar homeostasis was studied in fasted rats. When carbachol, muscarine, bethanechol, methacholine, or neostigmine was injected into the third cerebral ventricle, it caused a dose-dependent increase in the hepatic venous plasma glucose concentration. However, in the case of 1,1-dimethylphenyl-4-piperazinium iodide (DMPP) or nicotine, the level of hepatic venous glucose did not differ from that of the saline-treated control rats. The increase in glucose level caused by neostigmine was dose-dependently suppressed by coadministration of atropine. These facts suggest that cholinergic activation of muscarinic receptors in the CNS plays a role in increasing hepatic glucose output. Injection of neostigmine (5 X 10(-8) mol), an inhibitor of cholinesterase, into the ventricle resulted in the increase of not only glucose, but also glucagon, epinephrine, and norepinephrine in the hepatic venous plasma. However, constant infusion of somatostatin through a femoral vein completely prevented the increase of glucagon after administration of neostigmine, although the increase of hepatic venous glucose and epinephrine levels were still observed. Neostigmine-induced increments in glucose did not occur in adrenalectomized rats. This suggests that the secreted epinephrine acts directly on the liver to increase hepatic glucose output.

Olanzapine-Induced Hyperglycemia: Possible Involvement of Histaminergic, Dopaminergic and Adrenergic Functions in the Central Nervous System

“…It is previously reported that the nonselective muscarine receptor agonists increase blood glucose levels, indicating that central muscarine receptors positively regulate blood glucose levels [37]. The present study showed that muscarinic M 1 receptor antagonist dicyclomine did not affect the blood glucose levels.…”

The Roles of Glucagon and Adrenal Epinephrine in Mediating Hyperglycemia Induced by Third Cerebroventricular Injection of Bombesin.

“…Although it has not yet been thoroughly clarified whether or not somatostatin itself directly affects the rates of either glucose uptake or glucose production (Cherrington et al ., 1977;Sacca et al, 1979), our previous report (Iguchi et al, 1986) demonstrated that the hyperglycemic response to endogeneously secreted epinephrine is not influenced by this constant somatostain infusion . Furthermore, bombesin-induced hyperglycemia was not observed in bilateral adrenalectomized rats with constant somatostatin infusion , supporting the theory that the hyperglycemic response to bobesin is dependent on the secretion of epinephrine.…”

“…We recently reported that neostigmine injected into the third cerebral ventricle stimulated the secretion of epinephrine, which in turn resulted in producing hyperglycemia in the absence of a rise in the plasma glucagon concentration during constant intravenous infusion of somatostatin (Iguchi et al, 1986). Thus, the present study was aimed to further examine whether bombesin-induced central hyperglycemia was due to secreted einephrine itself, or mediated via epinephrine-stimulated glucagon secretion.…”

Mechanism of Intrahippocampal Neostigmine-lnduced Hyperglycemia in Fed Rats

“…IRG was measured by radioimmunoassay according to the method described previously [5]. The plasma levels of epinephrine and norepinephrine were determined using high-performance liquid chromatography with electrochemical detector as described pre viously [6], After the experiments, the animals were killed and their brains were fixed with 20% formalin for histologic examination. Proper placement of the needles and the correctness of the lesioned areas was histologically confirmed [7].…”