ALTERED ACTIVITY OF THE AUTONOMOUS NERVOUS-SYSTEM AS A DETERMINANT OFTHE IMPAIRED BETA-CELL SECRETORY RESPONSE AFTER PROTEIN-ENERGY RESTRICTION IN THE RAT

Glucose-induced insulin secretion in vivo is known to be severely blun ted in the rat as a consequence of protein-energy restriction starting early in life. We have recently reported in such malnourished rats (M rats) that the release of the counterregulatory hormones that defend against hypoglycemia was severely disturbed, and their plasma levels o f epinephrine and norepinephrine were prominently increased. Knowing t hat the autonomic nervous system has the potential to play a major rol e in the control of insulin secretion in response to glucose in vivo, we therefore determined whether protein-energy restriction starting af ter weaning could alter sympathetic and/or parasympathetic nerve activ ities, and whether these changes could be responsible for the lack of response to glucose of their beta-cells in vivo. When tested in the ba sal postabsorptive state, the malnourished rats exhibited profound alt erations of both parasympathetic and sympathetic nerve activities; the firing rates of the vagus nerve and the superior cervical ganglion we re dramatically decreased and increased, respectively. Under the same conditions, insulin secretion in vivo in response to a glucose load (D elta I/Delta G) was severely decreased in M rats compared with that in control (C) rats. When evaluated after administration of acetylcholin e, Delta I was amplified to the same extent in M rats as in C rats. Af ter administration of the alpha(2A)-adrenergic agonist oxymetazoline, glucose-induced insulin release in M rats was not significantly affect ed, whereas it was sharply decreased in C rats. Finally, administratio n of yohimbine, an alpha(2)-adrenergic antagonist, partially restored the lack of reactivity of the beta-cells to glucose in the M rats, as Delta I/Delta G was amplified by g-fold in the M group and by 3.3-fold in the C group. We conclude that protein-energy restriction starting early in life in rats brings about changes in the overall activity of the autonomic nervous system that, in turn, are responsible at least i n part for the acquisition/maintenance of decreased beta-cell reactivi ty to glucose in vivo.