ABSTRACT
The mechanism of disopyramide-induced hypoglycemia, a life-threatening complication in the antiarrhythmic drug treatment, is still controversial. To elucidate this, we have evaluated plasma insulin (IRI) and glucagon (IRG) responses in the pancreatic vein (PV) of the in situ pancreas as well as responses of plasma IRI, IRG, and glucose in the femoral artery (FA) to disopyramide phosphate administration in anesthetized dogs. First, infusion of disopyramide at a dose of 50 mg for ten minutes directly into the pancreatic artery, but not the vehicle, increased significantly plasma IRI concentration in the PV (P less than .05 or less), where the IRI response started within three minutes and reached a peak of 2.8-fold preinfusion value at 30 minutes after starting the infusion (n = 7). Plasma IRI concentration in the FA also increased slightly but significantly (P less than .05). Plasma IRG concentration in the PV initially decreased significantly (P less than .05 or less) and in the FA at one point (P less than .05) during the infusion, and then increased significantly after cessation of the infusion, showing a peak of 1.9-fold preinfusion value at 60 minutes in the PV and the FA (P less than .05). Plasma glucose concentration in the FA decreased slowly and significantly after the infusion (P less than .05 or less) and fell by 16% of the baseline value at 60 minutes (P less than .05). Second, serum disopyramide concentration of 13.7 +/- 2.8 micrograms/mL at ten minutes, which corresponds to a twofold to threefold concentration of the human therapeutic level (n = 4).(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Blood Glucose/metabolism , Disopyramide/pharmacology , Insulin/metabolism , Islets of Langerhans/metabolism , Animals , Dogs , Glucagon/blood , Glucagon/metabolism , Insulin/blood , Insulin Secretion , Islets of Langerhans/drug effects , Kinetics , Reference ValuesABSTRACT
To investigate whether somatostatin, one of the pancreatic islet hormones, influences the afferent firing activity of the vagus innervating the pancreas and whether there is any relevant morphological basis for the electrophysiological event, cyclic somatostatin-14 was injected into the rat pancreatic artery. The somatostatin injection at a physiological (0.61 pmol) or a pharmacological (3.05 pmol) dose significantly increased the afferent firing discharge rate of the pancreatic vagus in rats anesthetized with urethan and chloralose. The present histological examination disclosed a glomuslike neurovascular body in the rat peripancreatic sinusoidal vein. The body included many small corpuscles, and the corpuscle contained a structure like the afferent nerve ending. The immunohistochemical study revealed that the structure preferentially bound exogenous somatostatin. These electrophysiological and histological findings suggest that the vagal pancreatic nerve is receptive to somatostatin and that there exists a local neural monitoring system for somatostatin secreted from the islets.
Subject(s)
Pancreas/innervation , Somatostatin/physiology , Vagus Nerve/physiology , Afferent Pathways/drug effects , Afferent Pathways/physiology , Animals , Electrophysiology , Histocytochemistry , Immunochemistry , Male , Pancreas/anatomy & histology , Rats , Rats, Inbred Strains , Somatostatin/pharmacology , Vagus Nerve/drug effectsABSTRACT
An intraportal bolus injection of cyclic somatostatin in a dose of 3.05 pmol significantly increased the vagal afferent discharge rate in the rat. The results indicate that somatostatin facilitates the vagal sensory nerve activity in the portal venous area. The present immunohistochemical examination of the rat hepatic neural system further disclosed the encapsulated corpuscles which showed intense staining for exogenous somatostatin. They were located beneath the endothelium of the large branches of the portal vein, protruded into the lumen and contained terminal nerve arborizations in the core.
