Central suppressive effect of octreotide the hyperglycemic response to 2-deoxy-D-glucose injection or cold-swim stress in awake rats: possible mediation role of hypothalamic noradrenergic drive

Somatostatin (SRIH) and its analog have been reported to act within the cen tral nervous system to suppress the hyperglycemic response to a variety of neural stimuli. On the other hand, the hyperglycemic response to 2-deoxy-D- glucose (2-DG) injection or cold-swim stress is well demonstrated to be clo sely associated with an increase in hypothalamic noradrenergic neuronal act ivity (NNA). To evaluate whether the suppression of the hypothalamic NNA re sponse could be involved in the central mechanism whereby a SRIH analog inh ibits the hyperglycemic response, octreotide, a clinically used long-acting octapeptide SRIH analog, was administered into the third cerebral ventricl e of awake rats prior to the intraperitoneal injection of 2-DG or cold-swim stress. Hypothalamic noradrenaline (NA) and its neuronal metabolite, 3,4-d ihydroxyphenylethyleneglycol (DHPG). were analyzed, and the ratio of DHPG t o NA was used as an index of NNA. Intracerebroventricular (i.c.v.) pretreat ment with octreotide suppressed the 2-DG-induced increase in hypothalamic N NA, accompanied by the inhibition of the serum glucose, NA and adrenaline r esponses. This suppressive effect of octreotide was dose-dependent. Similar ly, i.c.v. pretreatment with octreotide prevented the hypothalamic NNA resp onse to cold-swim stress, accompanied by a blockade of the increases in ser um glucose, NA and adrenaline. A close relationship between hypothalamic NN A and serum glucose emerged from these studies. Intraperitoneal pretreatmen t with octreotide had no significant effect on the hyperglycemic or hypotha lamic NNA response to 2-DG injection. These findings suggest that the inhib itory effect of octreotide on the hypothalamic NNA response to 2-DG injecti on or cold-swim stress is associated with the simultaneous suppression of t he hyperglycemic response. Supporting the concept that hypothalamic NNA con tributes to the modulation of blood glucose in stressful conditions, it is suggested that the suppression of the hypothalamic NNA response is, at leas t in part, involved in the central mechanism by which octreotide inhibits t he hyperglycemic response to 2-DG injection or cold-swim stress. (C) 2001 E lsevier Science B.V. All rights reserved.