Somatostatin, a hypothalamic peptide that inhibits the secretion of pituitary growth hormone, inhibits basal insulin secretion in fasted cats and rats. In fasted baboons both basal and arginine-stimulated secretion of insulin and glucagon are inhibited. Somatostatin appears to act directly on the endocrine pancreas. The action is dose-related, rapid in onset, and readily reversed.

In overnight fasted rhesus monkeys, synchronous, regular oscillations occurred in the plasma concentrations of glucose, insulin, and glucagon. The oscillations displayed a period averaging 9 minutes. The amplitudes for insulin and glucagon were ten and five times greater than for glucose. Insulin cycled in and glucagon out of phase with glucose. In baboons, oscillations of glucose and insulin were smaller than in rhesus monkeys, while in man, regular oscillations were not observed.

A B S T R A C T The nature and extent of somatostatininduced inhibition of pancreatic endocrine secretion were studied by administration of a number of stimuli of either glucagon or insulin to overnight fasted baboons with and without an infusion of linear somatostatin. The stimuli for acute-phase insulin release were intravenous pulses of glucose, tolbutamide, isoproterenol, and secretin. When given 15 min after the start of a somatostatin infusion, these agents were essentially unable to stimulate insulin secretion. Chronic insulin secretion was stimulated by infusions of either glucose or glucagon. Within 10 min of the start of a superimposed infusion of somatostatin, insulin levels fell to less than 40% of prestimulus control and remained suppressed for the duration of the somatostatin infusion. Stimulation of glucagon secretion by insulin-induced hypoglycemia was also blocked by somatostatin.Plasma glucose decreased during somatostatin infusions except when superimposed upon an infusion of glucagon. Somatostatin had no effect on glucose production in a rat liver slice preparation.We conclude: (a) Somatostatin is a potent and so far universally effective inhibitor of both acute and chronic phases of stimulated insulin and glucagon secretion (b) The inhibitory effect is quickly reversible and the pattern of recovery of secretion is appropriate to prevailing signals; (c) Present evidence suggests that the effect of somatostatin on blood glucose is mediated through its effect on blood glucagon; (d) In the overnight-fasted baboon both in the basal state and 45 min into a 4-mg/kg min glucose infusion, a somatostatininduced fall in serum insulin levels appears to be unable to prevent a decrease in hepatic glucose production.

1The Na', K+-pump has been implicated in animal models of airway hyperreactivity. We examined the effects of inhibiting the Na', K+-pump and Na+, Ca2+-exchange on isometric tone of isolated trachealis from humans and other species. 2 In preparations from 5 out of 9 humans, strong spontaneous contractions (36-48 h-'; up to 1.8 g) developed within 25 min. 3 Ouabain (10-7-10-'M) caused an immediate and sustained contraction. This response was not blocked by atropine, diphenhydramine, or cimetidine. 4 Contractions were also elicited when the normal physiological solution was changed to a K+-free solution, a procedure which inhibits the Na+, K+-pump, and in reduced (15 mM) Na+ solution, which inhibits Na+, Ca2+ exchange. 5 In preparations of dog and guinea-pig isolated trachea, ouabain (10-M) caused a multiphasic response; in the rabbit, ouabain was without effect. K+-free solution was without effect in the dog preparations and produced relaxation of the guinea-pig trachea. Guinea-pig tracheae responded to a low Na+ solution with a strong contraction. 6 Our findings indicate that: (a) human airway smooth muscle may be a spontaneously contracting muscle, at least in vitro, (b) a prolonged contraction to ouabain is unique for the human airway smooth muscle among the animals tested, as is the contraction in a K+-free medium, and (c) the contractile response does not involve acetylcholine or histamine release, but may involve a Na+, Ca2+-exchange mechanism. These results suggest that the level of Na+, K+-pump activity could play a role in determining the degree of bronchomotor tone in humans.

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