Hyperglycemic Effect of Neurotensin, a Hypothalamic Peptide*

Abstract

A hypotensive, gut-contracting peptide, neurotensin (NT), recently isolated from bovine hypothalami, produced hyperglycemia within minutes after i.v. injection into anesthetized rats. The dose-response relationship (.DELTA.glucose, 15 min after injection) was linear over the range 30-200 pmol/100 g body wt. NT did not alter the disappearance rate of [14C]glucose from plasma during the development of the hyperglycemia. The peptide caused a fall in liver glycogen (52 .+-. 6.5 to 41 .+-. 3.3 mg/g) and a 7-fold increase in the activity of the 5''-AMP independent form of liver glycogen phosphorylase. Activation of liver glycogen phosphorylase did not occur in vitro under conditions found suitable for demonstrating the effectiveness of glycagon, suggesting the possible involvement of an intermediary substance(s) in vivo. Acute adrenalectomy did not prevent the response. Hypophysectomized rats (4 days postoperative) were less sensitive to NT, perhaps as a consequence of their diminished liver glycogen levels (normal, 52 .+-. 6.5 mg/g; hypophysectomized, 23 .+-. 2.8 mg/g); the presence of the pituitary was not essential for this response. NT was also effective in rats with hereditary diabetes insipidus (Brattleboro strain). At the time intervals sampled, radioimmunoassayable plasma levels of growth hormone, glucagon and insulin were not significantly changed after injection of NT into normal rats. Pretreatment of rats with reserpine (7 mg/kg), morphine sulfate (10 mg/kg), propranolol (5 mg/kg) or phenoxybenzamine (10 mg/kg) did not prevent the response. These findings characterize the action of NT on liver glycogen metabolism and blood glucose levels, but a physiological role for NT in this regard remains to be demonstrated.