Metabolic effects of adrenaline and noradrenaline in man: studies with somatostatin

The metabolic responses to infusion of adrenaline (6 micrograms/min) and of noradrenaline (5 micrograms/min) for 120 minutes have each been studied in five normal males with and without concurrent somatostatin (250 micrograms/h). Adrenaline induced marked and sustained hyperglycaemia (maximal blood glucose at 75 min, 9.0 +/- 0.4 mmol/l) while noradrenaline induced only a mild and transient blood glucose rise. Blood lactate was elevated by adrenaline (2.57 +/- 0.47 mmol/l with adrenaline, 0.62 +/- 0.06 mmol/l with saline at 120 min, p less than 0.02). Pyruvate levels rose proportionately less so that the circulating lactate:pyruvate ratio was increased (16.6 +/- 1.3 with adrenaline, 11.4 +/- 0.9 with saline at 120 min, p less than 0.05). Lactate and pyruvate levels were unaffected by noradrenaline. Both catecholamines increased circulating non-esterified fatty acid (NEFA) and glycerol to peak at 30 min, while maximal 3-hydroxybutyrate concentrations were achieved at 50 min (0.26 +/- 0.07 mmol/l with adrenaline; 0.23 +/- 0.06 mmol/l with noradrenaline; 0.03 +/- 0.01 mol/l with saline, both p less than 0.05). Insulin levels were partially suppressed by noradrenaline, while a small rise in circulating insulin was observed with adrenaline which was also associated with a large rebound rise in insulin secretion on cessation of the infusion. Mild and transient hyperglucagonaemia was observed with adrenaline while stimulation of glucagon secretion was more sustained with noradrenaline. Somatostatin suppressed insulin, glucagon and growth hormone secretion and both magnified and prolonged the hyperglycaemic effect of adrenaline (maximal at 105 min, 11.3 +/- 0.5 mmol/l, p less than 0.01 versus adrenaline alone).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of the octapeptide of cholecystokinin on insulin and glucagon secretion in the dog.

The effects of intravenous infusion of synthetic C-terminal octapeptide of cholecystokinin (OP-CCK) on concentrations of insulin and glucagon in peripheral venous plasma of conscious dogs were studied. Both hormones increased in response to 160 and 480 ng/kg/h of OP-CCK. The increases to 480 ng/kg/h were larger than those to 160 ng/kg/h. Peripheral venous concentrations of glucose and intestinal glucagon-like immunoreactivity were not altered by OP-CCK. OP-CCK, 160 ng/kg/h, did not enhance insulin and glucagon responses to intravenous infusion of amino acids. The results suggest that insulin- and glucagon-releasing actions of porcine cholecystokinin preparations should not be attributed entirely to gastric inhibtory polypeptide or other impurities contained in these preparations since the synthetic active fragment of cholecystokinin alone increases insulin and and glucagon concentrations in peripheral plasma.     

The effects of epinephrine on islet hormone secretion in the dog

We investigated the direct effects of physiological levels of epinephrine on the basal and arginine-stimulated secretion of insulin, glucagon, and somatostatin from the in situ pancreas in halothane-anaesthetized dogs. An IV infusion of 20 ng/kg/min of epinephrine increased plasma epinephrine levels to 918 +/- 103 pg/ml (P less than 0.001), and increased the baseline pancreatic output of insulin (P less than 0.05), glucagon (P less than 0.05) and somatostatin (P less than 0.05). The acute insulin response (AIR) to 2.5 g of arginine during this infusion of epinephrine was significantly higher (P less than 0.05) than in controls as were the acute glucagon response (AGR) (P less than 0.05) and the acute somatostatin response (ASLIR) (P less than 0.05). Plasma glucose levels increased slightly and transiently during infusion of epinephrine from 99 +/- 2 mg/dl to a maximum of 110 +/- 3 mg/dl (P less than 0.05). An IV infusion of 80 ng/kg/min of epinephrine produced plasma epinephrine levels of 2,948 +/- 281 pg/ml, and increased the baseline pancreatic output of insulin (P less than 0.05) and glucagon (P less than 0.05). In contrast, baseline somatostatin output decreased transiently during this high dose infusion of epinephrine. The AIR and ASLIR to arginine were both significantly lower (P less than 0.05) than those during the infusion of epinephrine at the low dose. The AGR to arginine remained potentiated (P less than 0.05). Plasma glucose levels increased from 99 +/- 3 mg/dl to 119 +/- 4 mg/dl (P less than 0.01). We conclude that the effect of epinephrine on islet hormone secretion is dependent on the plasma level of epinephrine. At stress levels of 900-1000 pg/ml, both insulin and somatostatin secretion are stimulated; only at near pharmacologic, or extreme stress levels, does epinephrine produce net inhibition.     

The effects of epinephrine on islet hormone secretion in the dog

Summary We investigated the direct effects of physiological levels of epinephrine on the basal and arginine-stimulated secretion of insulin, glucagon, and somatostatin from the in situ pancreas in halothane-anaesthetized dogs. An IV infusion of 20 ng/kg/min of epinephrine increased plasma epinephrine levels to 918±103 pg/ml (P<0.001), and increased the baseline pancreatic output of insulin (P<0.05), glucagon (P<0.05) and somatostatin (P<0.05). The acute insulin response (AIR) to 2.5 g of arginine during this infusion of epinephrine was significantly higher (P<0.05) than in controls as were the acute glucagon response (AGR) (P<0.05) and the acute somatostatin response (ASLIR) (P<0.05). Plasma glucose levels increased slightly and transiently during infusion of epinephrine from 99±2 mg/dl to a maximum of 110±3 mg/dl (P<0.05). An IV infusion of 80 ng/kg/min of epinephrine produced plasma epinephrine levels of 2948±281 pg/ml, and increased the baseline pancreatic output of insulin (P<0.05) and glucagon (P<0.05). In contrast, baseline somatostatin output decreased transiently during this high dose infusion of epinephrine. The AIR and ASLIR to arginine were both significantly lower (P<0.05) than those during the infusion of epinephrine at the low dose. The AGR to arginine remained potentiated (P<0.05). Plasma glucose levels increased from 99±3 mg/dl to 119±4 mg/dl (P<0.01). We conclude that the effect of epinephrine on islet hormone secretion is dependent on the plasma level of epinephrine. At stress levels of 900–1000 pg/ml, both insulin and somatostatin secretion are stimulated; only at near pharmacologic, or extreme stress levels, does epinephrine produce net inhibition.     

Quantitation of inhibition of gastric electrolyte secretion by insulin in the dog

Summary Inhibition of gastric juice volume, acid, and chloride output by insulin injected during histamine infusion in dogs has been shown to depend on the dose of insulin. Thus, 0.15 U./kg. did not inhibit secretion, while 0.3 U./kg. did so in some dogs. Doses of 0.45 U./kg. or greater always inhibited up to 100%.When the observed deficit in acid output from these experiments was added to the observed acid output after the various doses of insulin, expected curves of acid output paralleled the curves of blood-sugar depression.The magnitude and timing of inhibition are a simple explanation of the progressively smaller and more bimodal acid output curves with increasing doses of insulin.Supported by Grants CA 04980, AM 09260, and 2A-5286 from the U. S. Public Health Service.The author is indebted to Miss Mary L. Collins, Mr. Robert Harris, and Mrs. Theo Altes, for their expert help.     

Acute effects of insulin on cardiovascular function and noradrenaline uptake and release

Non-enzymatic glycosylation of tissue and haemolysate proteins has been studied in normal and diabetic rats by reduction with tritiated sodium borohydride (NaB3H4) alone or in combination with chromatography on m-aminophenylboronic acid coupled to Biogel P-6. With NaB3H4 reduction alone, there was a linear relationship between plasma glucose and tritium incorporation into haemolysate protein. However, increased non-enzymatic glycosylation of tissue protein could not be demonstrated with NaB3H4 reduction alone. Tritiated glycosylated amino acids could be selectively removed by m-aminophenylboronic acid immobilized on Biogel P-6, then eluted by acidification and the radioactivity in the acidic peak used to estimate non-enzymatic glycosylation. Using the combined techniques, an increase in non-enzymatic glycosylation was observed in heart, kidney and liver obtained from rats with diabetes of 18 weeks duration.