INVOLVEMENT OF THE AUTONOMIC NERVOUS-SYSTEM IN THE IN-VIVO MEMORY TO GLUCOSE OF PANCREATIC BETA-CELL IN RATS

The fact that the potentiating effect of prolonged hyperglycemia on th e subsequent insulin secretion is observed in vivo but not in vitro su ggests the involvement of extrapancreatic factors in the in vivo memor y of pancreatic beta cells to glucose. We have investigated the possib le role of the autonomic nervous system. Rats were made hyperglycemic by a 48-h infusion with glucose (HG rats). At the end of glucose infus ion as well as 6 h postinfusion, both parasympathetic and sympathetic nerve activities were profoundly altered: parasympathetic and sympathe tic activities, assessed by the firing rate either of the thoracic vag us nerve or the superior cervical ganglion, were dramatically increase d and decreased, respectively, Moreover, 6 h after the end of glucose infusion, insulin secretion in response to a glucose load was dramatic ally increased in HG rats compared to controls. To determine whether t hese changes could be responsible for the increased sensitivity of the beta cell to glucose, insulin release in response to glucose was meas ured in HG and control rats, either under subdiaphragmatic vagotomy or after administration of the alpha(2A)-adrenergic agonist oxymetazolin e. Both treatments partially abolished the hyperresponsiveness of the beta cell to glucose in HG rats. Therefore chronic hyperglycemia bring s about changes in the activity of the autonomic nervous system, which in turn are responsible, at least in part, for the generation of enha nced beta cell responsiveness to glucose in vivo.