The fact that the potentiating effect of prolonged hyperglycemia on the subsequent insulin secretion is observed in vivo but not in vitro suggests the involvement of extrapancreatic factors in the in vivo memory of pancreatic 1 cells to glucose. We have investigated the possible role of the autonomic nervous system. Rats were made hyperglycemic by a 48-h infusion with glucose (HG rats). At the end of glucose infusion as well as 6 h postinfusion, both parasympathetic and sympathetic nerve activities were profoundly altered: parasympathetic and sympathetic activities, assessed by the firing rate either of the thoracic vagus nerve or the superior cervical ganglion, were dramatically increased and decreased, respectively. Moreover, 6 h after the end of glucose infusion, insulin secretion in response to a glucose load was dramatically increased in HG rats compared to controls. To determine whether these changes could be responsible for the increased sensitivity of the 13 cell to glucose, insulin release in response to glucose was measured in HG and control rats, either under subdiaphragmatic vagotomy or after administration of the ae2A-adrenergic agonist oxymetazoline.Both treatments partially abolished the hyperresponsiveness of the .3 cell to glucose in HG rats.Therefore chronic hyperglycemia brings about changes in the activity of the autonomic nervous system, which in turn are responsible, at least in part, for the generation of enhanced f3 cell responsiveness to glucose in vivo. (J. Clin.

This work was designed to study the effects of insulin secretion and action in vivo of moderate hyperglycemia induced by glucose infusion during 4 days in unrestrained rats. The maintenance of a glycemia around 170 mg/dl throughout the infusion time necessitated a gradual increase of glucose infusion rate from 11.5 to 19 g/day. Throughout the infusion period, plasma insulin-to-glucose ratio remained much higher in hyperglycemic rats (HG) than in controls. Glucose tolerance and insulin secretion tests were performed 2 h after the end of the infusion, when glycemia and insulinemia were back to basal values. Incremental plasma glucose values were significantly lower in HG than in control rats without significant changes in incremental plasma insulin concentrations, suggesting an increased insulin efficiency. At the same insulin level, glucose utilization was higher in HG than in control rats during euglycemic-hyperinsulinemic clamps. These data show that short-term hyperglycemia and hyperinsulinemia do not induce a defect in insulin secretion in vivo and do increase tissue sensitivity to insulin.

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