Arginine In Man Research Articles

Insulin-induced hypoglycemia, l-dopa and arginine stimulate GH secretion through different mechanisms in man

We sought to clarify the mechanisms of growth hormone (GH) secretion induced by insulin hypoglycemia, l-dopa, and arginine in man. The secretion of GH as measured by increased plasma level, in response to oral administration of 500 mg l-dopa or 30 min-infusion of arginine, was not modified by prior intravenous administration of 200 μg GH-releasing hormone (GHRH). It was, however, completely blocked by preadmininstered 50 μg SMS201-995, a long-acting somatostatin (SRIH) analog. GH release with 200 μg GHRH was completely blocked by 100 μg SMS201-995. GH secretion caused by insulin-induced hypoglycemia was significantly reduced but still present after administration of 100 μg of the analog. These results suggest that a suppression of SRIH release may be partially involved in the stimulatory mechanism of GH secretion by l-dopa. Coadministration of GHRH accentuated the stimulatory effect of arginine on GH secretion. Arginine significantly raised plasma TSH levels. These findings suggest that arginine suppresses SRIH release from the hypothalamus to cause GH secretion because SRIH suppresses TSH secretion. It is also suggested that some factor (or factors) other than GHRH and SRIH are involved in the mechanism by which insulin-induced hypoglycemia stimulates GH secretion, because the effect of insulin was not fully blocked in the presence of SRIH analog. Thus all the tests for GH release appear to act via different mechanisms.

Participation of cholinergic muscarinic receptors in glucagon- and arginine-mediated growth hormone secretion in man.

To investigate the participation of cholinergic receptors in glucagon- and arginine-induced GH and PRL secretion, glucagon (1 mg, sc) and arginine (30 mg over 30 min) were administered to a group of normal subjects. On a different occasion, both tests were repeated after premedication with 40 mg pirenzepine, a muscarinic blocker, given iv 5 min before the test substances. Pirenzepine completely suppressed the glucagon- and arginine-induced GH rise in all subjects. The PRL response to arginine was not altered by pirenzepine. The results suggest that cholinergic muscarinic receptors regulate the GH response to glucagon and arginine in man.

The hypophosphatemic and hyperkalemic effect of arginine in man.

The effects of a 0.5 g/kg body weight arginine infusion on plasma inorganic phosphate and potassium were examined in 15 normal subjects, and 6 recently diagnosed insulinopenic diabetics. Plasma phosphorus displayed a highly significant (p less than 0.001) fall in normal subjects, with a maximum fall below the baseline of 1.11 +/- 0.15 mg/100 ml or 33 + 3% (mean +/- SE). In addition, there was a highly significant correlation (p less than 0.01) between these falls and the insulin peaks induced by arginine. Plasma potassium levels, on the other hand, displayed a distinct and significant increase in 7 of the 8 subjects studied in this connection. The maximum increase over the baseline was 1.23 +/- 0.17 meq/l or 33 +/- 6% (p less than 0.01). In diabetic patients, arginine too led to a fall in phosphorus. While this was still significant, it was clearly less than in normal subjects: maximum fall = 0.64 +/- 0.09 mg/100 ml or 15 +/- 3%. Plasma potassium increased to a greater extent than in normal subjects: maximum increase = 1.63 +/- 0.21 meq/l or 42 +/- 6%. These findings show that arginine is responsible for a fall in plasma phosphorus that may well be partly related to the insulin response, and an increase in plasma potassium of clinical significance, whose mechanism(s), however, are still obscure.

Inhibition by indomethacin of the glycemic response to arginine in man.

We investigated the effect of indomethacin on the glucagon, glucose, and insulin responses to arginine in eight normal subjects. Glucagon secretion was not affected, but glucose and insulin responses were significantly decreased. Although inhibition of hepatic glycogenolysis is a possible reason for this effect, hepatic glycogen depletion and augmented peripheral glucose utilization are other explanations to be considered.

Xylitol: stimulation of insulin and inhibition of glucagon responses to arginine in man.

The effect of intravenous xylitol infusions on plasma glucagon and insulin responses to intravenous arginine infusions (30 g for 45 min) or arginine "pulses" (4 g for 2 min) was studied in normal subjects. Intravenous infusion of arginine caused biphasic increases in plasma glucagon and insulin in all subjects studied. The increase in plasma glucagon induced by arginine infusion was significantly reduced by xylitol infusions started at 45 min before arginine infusion, irrespective of virtually unchanged blood glucose levels. Plasma insulin response to arginine was exaggerated by xylitol infusion. Repeated arginine pulses given at 30 min intervals evoked uniphasic and almost identical rises of plasma insulin and glucagon with each pulse. Intravenous xylitol infusions significantly blunted plasma glucagon responses and augumented the plasma insulin response to arginine pulses, despite only slight elevations of plasma glucose. These results suggest that xylitol has an inhibitory effect on both basal and arginine-stimulated glucagon secretion, while it enhances insulin secretion.

The Glycemic Response to Arginine in Man

To determine the mechanism of the glycemic response to administration of arginine in man, incorporation of arginine-U-C-14 into blood glucose was investigated in postabsorptive subjects given an intravenous infusion of 30 gm. of Larginine monochloride containing 50 μCi of L-arginine-UC-14. As expected, a prompt increase in blood glucose and serum insulin levels was observed. However, whereas the maximal increment in blood glucose of 15 to 22 mg./100 ml. occurred within twenty to thirty minutes of initiation of the infusion, recovery of arginine-C-14 in blood glucose was not detectable until after thirty to fifty minutes, reaching peak levels at 120 min. In subjects given only the tracer dose of arginine-C-14 in whom serum insulin concentration remained at postabsorptive levels, incorporation of C-14 into blood glucose was detectable within ten minutes. It is concluded that the glycemic effect of arginine cannot be explained on the basis of gluconeogenesis from this amino acid. The insulinogenic action of arginine may contribute to the delay in incorporation of this amino acid into glucose.

Arginine-induced insulin release in relation to the cyclic AMP system in man.

The insulin-releasing action of the amino acid arginine in man is inhibited by hypoglycemia. Furthermore, arginine potentiates glucose-induced insulin release, probably by amplifying the insulinogenic signal evoked by glucose in the beta-cell. The beta-adrenergic blocking agent propranolol, in doses known to suppress glucose-induced insulin release, did not alter insulin response to arginine infusion. Arginine markedly augments insulin release secondary to glucose whereas, under the same experimental conditions, it has no effect on insulin release secondary to glucagon. Finally, pretreatment with aminophylline potentiated the insulinogenic potency of the amino acid. We have previously postulated that glucose elicits insulin release by acting directly on a specific cell membrane receptor. The signal thus evoked is probably mediated through the adenyl cyclase-cyclic AMP system. In the light of this hypothesis and the above results we suggest that arginine acts on the beta-cell by amplifying the transmission...

The Adrenergic Modulation of the Serum Insulin Response to Intravenous Arginine in Man

Abstract. The effect of adrenergic stimulation and blockade on metabolic responses to arginine have been studied. Phentolamine enhanced, and adrenalin diminished, the rise in serum immunoreactive insulin that followed intravenous arginine; these effects were not secondary to changes in blood levels of arginine, glucose or free fatty acids following the amino acid infusion. Phentolamine did not affect the clearance of infused insulin from the blood stream. It was concluded that adrenergic receptor sites are involved in the modulation of the secretion of insulin in response to an infusion of arginine.

Effects of 2-deoxy-D-glucose on insulin-secretory responses to intravenous glucose, glucagon, tolbutamide and arginine in man.

The effects of prior administration of 2-deoxy-D-glucose on insulin secretory responses to insulin secretagogues were studied. Following 2-deoxy-D-glucose administration to eight subjects including two maturity-onset diabetics, the stimulatory effects of both glucose and glucagon were markedly obtunded by comparison with control studies in the same subjects. In another group of eight subjects including one maturity-onset diabetic, the mean plasma insulin responses to tolbutamide and arginine were only very slightly but not significantly reduced following 2-deoxy-D-glucose as compared to control studies. These results suggest that the inhibitory effect of 2-deoxy-D-glucose on insulin secretory responses to glucose and glucagon is not related to epineplirine discharge and that the mechanism of stimulation of insulin secretion does not follow identical pathways for all secretagogues.

Effects of secretin, pancreozymin, or gastrin on the response of the endocrine pancreas to administration of glucose or arginine in man.

Intravenous administration of porcine secretin or pancreozymin or synthetic human gastrin II resulted in raised increments in serum immunoreactive insulin during intravenous infusion of glucose in normal man. Enhancement of serum immunoreactive insulin by each hormone was associated with accelerated disposal of glucose. In response to prolonged intravenous infusion of arginine with pancreozymin there was a maintained rise in immunoreactive insulin and glucagon-like immunoreactivity in the blood. These effects of pancreozymin and arginine were not reproduced with secretin and arginine, and may have been due to the stimulation of glucagon secretion together with insulin by pancreozymin. Enteric infusion of hydrochloric acid, or stimulation of gastric acid secretion by betazole, presumed to cause release of endogenous secretin, led to enhancement of insulin secretion during intravenous infusion of glucose. Enteric infusion of arginine, presumed to cause release of endogenous pancreozymin, led to a rise in serum immunoreactive insulin not attributable to effects of circulating glucose and amino acids. It is concluded that secretin and pancreozymin released in response to physiological stimuli contribute to stimulation of the endocrine pancreas after ingestion of food.

Effects of cortisol and diethylstilbestrol on growth hormone release by rat pituitary in vitro.

The secretion of growth hormone in response to hypoglycemia and the administration of arginine in man has been shown to be greatly influenced by certain non-pituitary hormones. Corticosteroids decrease growth hormone response to these stimuli in man (1,2) while estrogens and the synthetic estrogenic compound diethylstilbestrol facilitate the release of growth hormone(3,4). The mechanism of action of these modifying effects has not been established. Corticosteroids have little effect on the concentration of growth hormone in the pituitary of the normal rat(5). If corticosteroids are administered during the induction of hypoglycemia, the expected drop in growth hormone content is inhibited(5). Estrogens on the other hand decrease the concentration of growth hormone even when compared to pair fed control rats(6).The modifying effects of estrogens and corticosteroids on growth hormone secretion could be exerted either at the level of the hypothalamus by affecting the secretion of the somatotropin releasing fa...