Mechanism of central hyperglycemic effect of cholinergic agonists in fasted rats.
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.
D000315:Adrenalectomy; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D004837:Epinephrine / Q000097:blood; D005934:Glucagon / Q000097:blood; D006503:Hepatic Veins; D006706:Homeostasis / Q000187:drug effects*; D007276:Injections, Intraventricular; D007328:Insulin / Q000097:blood; D008297:Male; D009388:Neostigmine / Q000494:pharmacology; D009638:Norepinephrine / Q000097:blood; D010277:Parasympathomimetics / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000494:pharmacology
D001786:Blood Glucose; D007328:Insulin; D010277:Parasympathomimetics; D009388:Neostigmine; D013004:Somatostatin; D005934:Glucagon; D009638:Norepinephrine; D004837:Epinephrine