EFFECTS OF SUBSTANCE-P AND NEUROTENSIN INFUSED INTRA-PANCREATICALLY ON GLUCAGON AND INSULIN-SECRETION

Either synthetic substance P or synthetic neurotensin was infused at a dose of 20 pmol/kg/min for 10 min into the cranial pancreaticoduodenal artery in anesthetized dogs. During the infusion of substance P, blood flow and plasma concentrations of both glucagon and insulin in the cranial pancreaticoduodenal vein were briskly enhanced, indicating a great augmentation of bihormonal output. These parameters increased more slowly during the infusion of neurotensin. A delayed rise in plasma insulin was seen in the femoral artery, whereas no significant increase in arterial plasma glucagon was elicited during administration of both polypeptides. A significant rise in the arterial plasma glucose level occurred during their infusion. Intrapancreatic pretreatment with baclofen, a suppressor of spinal monoand polysynaptic reflexes (2 nmol/kg/min), or pretreatment with propranolol (0.02 mg/kg/min) did not suppress any of the responses to substance P. However, pretreatment with propranolol inhibited the neurotensin-induced enhancement in pancreatic venous blood flow and bihormonal secretion. These results suggest that endogenously released substance P and neurotensin may stimulate both glucagon and insulin secretion, that the stimulatory effect of substance P may not be exerted via any activation of the nervous system localized in the endocrine pancreas, and that the β-adrenergic receptor system may be involved in the mechanisms of neurotensin-stimulated secretion of glucagon and insulin. © 1978 by The Endocrine Society.