METABOLIC EFFECTS OF CATECHOLAMINES IN SHEEP By J. M. BAssETT*

Intravenous infusion of 1· 5 mg adrenaline over 30 min into adult Merino wethers (50 kg body weight), increased glucose, lactate, and free fatty acid (FFA) concentrations in plasma much more than did a single rapid intravenous injection of the same amount. There was no increase in plasma insulin concentration during adrenaline infusion or after adrenaline injection. There was a logarithmic relationship between the rate of adrenaline infusion and the increment in plasma concentrations of glucose and lactate during the first 30min of infusion. Infusion of adrenaline at either 0'0125, 0'025, 0'125, or 0·25 ",mole/min caused very large increases in FF A concentrations and prevented any increase in the plasma insulin concentration. Cessation of infusion was followed by a rapid increase in plasma insulin. Infusion of noradrenaline (0'025 ",mole/min) caused a substantial, but smaller, increase in FF A than the same dose of adrenaline and almost no change in glucose or lactate concentrations. Noradrenaline prevented any increase in insulin concentration when glucose was infused at the same time. Isoprenaline (0' 025 ",mole/min) caused greater increases in FFA but similar increases in lactate and much smaller increases in glucose than did adrenaline. In constrast to adrenaline and noradrenaline, isoprenaline greatly increased the plasma insulin concentration. This increase in insulin was greatly reduced when noradrenaline was infused with isoprenaline. The adrenergic blocking agent phentolamine completely prevented the inhibitory effect of adrenaline infused at a rate of O· 025 ",mole/min on insulin secretion, but only partly prevented it when adrenaline was infused at a rate of 0·125 ",mole/min. Phentolamine itself significantly decreased plasma glucose and increased plasma FFA. Neither phenoxybenzamine nor propranolol blocked the inhibitory effect of adrenaline on insulin secretion. Propranolol, but not phentolamine, inhibited the stimulation of insulin secretion by isoprenaline. Phentolamine, phenoxybenzamine, and propranolol all decreased the response of FF A to adrenaline infusion, but only phentolamine blocked its effect on plasma glucose. Propranolol blocked the increase in lactate caused by adrenaline. FFA mobilization and insulin secretion appear to be more sensitive to effects of the catecholamines than are glucose and lactate concentrations in sheep. The observations indicate that the effects of the catecholamines on insulin secretion in the sheep are similar to those in man and indicate that these inhibitory effects on the insulin-secretory mechanism occur with small physiological amounts of the hormones.