Bombesin, a peptide with widespread biological actions, has been demonstrated in human tissues by immunological methods. To investigate its effect in man, synthetic bombesin was infused at low doses in six male volunteers. Bombesin at 2.4 pmol kg-1 min-1 produced significant rises in plasma insulin, glucagon, pancreatic polypeptide, gastrin, cholecystokinin, motilin, glucose-dependent insulinotropic polypeptide, neurotensin, enteroglucagon, vasoactive intestinal polypeptide, and serum calcium. In contrast, bombesin caused a profound fall in parathyroid hormone levels and reduced plasma glucose concentrations. A late rise in plasma calcitonin was also observed. Bombesin had no significant effect on the pituitary hormones, TSH, GH, PRL, or cortisol. No hormonal changes or alterations in calcium were noted during saline infusions. Bombesin has a marked stimulatory effect on gastrointestinal hormones, which is unique and opposite to the effect of somatostatin, a potent inhibitor of gut hormone release. Bombesin also influences calcium-regulating hormones, either directly or through its action on gut hormones. The bombesin concentrations achieved with the dosages used were low enough to indicate a possible physiological role for the endogenous peptide.
Effects of total pancreatectomy on plasma glucagon, insulin and glucose responses to arginine were determined in 5 dogs. Portal vein and femoral artery samples were obtained in response to an arginine infusion (10 g/30 min) prior to, 1 h, 1 day and 1 week after pancreatectomy. Glucagon was measured using pancreatic-specific antiserum 30K (Unger, Dallas). Before pancreatectomy arginine significantly increased portal vein glucagon from 373 plus or minus 36 to 595 plus or minus 31 pg/ml and femoral artery levels from 233 plus or minus 28 to 342 plus or minus 74 pg/ml. Portal vein and femoral artery insulin concentrations of 74 plus or minus 21 and 17 plus or minus 3 muU/ml increased significantly to 173 plus or minus 64 and 31 plus or minus 7 muU/ml. Glucose levels did not change. One h after pancreatectomy, portal vein glucagon decreased to 121 plus or minus 15 pg/ml but increased to 230 plus or minus 42 pg/ml after arginine. Elevated blood glucose and the necessity for insulin treatment established the adequacy of pancreatectomy. Furthermore portal vein insulin levels were undetectable and unresponsive to arginine or a combination of glucose, glucagon, and tolbutamide 1 week after pancreatectomy. One day after pancreatectomy arginine significantly increased portal vein glucagon from 343 plus or minus 42 to 776 plus or minus 152 pg/ml. One week after pancreatectomy basal glucagon values were 374 plus or minus 30 in the portal vein and 360 plus or minus 49 in the femoral artery and responded to 1226 plus or minus 641 and 825 plus or minus 270 pg/ml, respectively, with arginine. Chromatography of plasma from one pancreatectomized dog on Sephadex G-50 after arginine stimulation revealed that much of the material cross-reacting with antibody 30K was eluted from the column earlier than either 125I-insulin or 125I-glucagon. In contrast, peak glucagon activity in plasma obtained from a normal human given arginine eluted from the column between the peak of 125I-insulin and 125I-glucagon; glucagon added to human plasma also was recovered in this same area between the 125I-insulin and 125I-glucagon peaks. These results suggest that some of the material that reacted with 30K antibody and which increased after pancreatectomy in response to arginine has a molecular weight greater than pancreatic glucagon. At autopsy no pancreatic tissue could be identified. Thus, after pancreatectomy, validated by absent insulin responses, the glucagon response to arginine was normal or increased. Since arginine is not thought to increase intestinal glucagon-like immunoreactive material, the source and nature of the material measured as glucagon after pancreatectomy is unknown, but may be important to any understanding of plasma glucagon measurements.
Hormone secretion by ten functionless human pituitary adenomas in cell culture has been measured, and compared with tissue immunocytochemistry and electron microscopy, as well as results with a normal pituitary. Patients presented following routine x-ray and had no clinical or biochemical endocrine abnormality apart form one male with raised serum FSH and PRL, normal LH, and low testosterone. Of the ten adenomas, nine secreted both LH and FSH in cell culture and five of these also secreted PRL, one did not secrete any anterior pituitary hormones (ACTH was not measured). No GH or TSH was detectable in the cultures of the nine LH/FSH secretors excluding the possibility of contamination by normal anterior pituitary. The normal pituitary cells secreted all anterior pituitary hormones: the amounts of FSH/LH being comparable with those of the adenomas. Immunostaining confirmed the cell culture results and showed the adenoma FSH/LH cells to be scattered singly or in small groups of two to five cells with both hormones usually being in the same cell. PRL where found was in separate cells. Hormone granules were small (50-160nm), round or irregular and scattered in the cytoplasm of rounded cell of low secretory activity. The negatively staining cells were not different ultrastructurally to those staining positively. It is concluded that a significant proportion of functionless pituitary adenomas have detectable low levels of LH/FSH secretion often accompanied by PRL when examined by cell culture or immunocytochemistry. Although these adenomas were endocrinologically quiescent activity could have been masked because of post-menopausal secretion and one male probably had and FSH-secreting adenoma.
Of 26 patients with active Cushing's syndrome assessed before and at three and 12 months after treatment, 21 had pituitary-dependent disease. Median urinary free cortisol values (per 24 hours) were 680, 180 and 200 nmol at zero, three and 12 months (normal less than 270 nmol), with significant improvement (P less than 0.001) at three and 12 months. Depression on the Hamilton rating scale was significantly less at three months (P less than 0.01) and at 12 months (P less than 0.001). We have already demonstrated that some patients with Cushing's syndrome have PSE diagnoses of depression and are more depressed than patients with other pituitary tumours. This is the firmest evidence to date that when Cushing's syndrome occurs it commonly causes depressive illness.
1 Pharmacokinetic and concentration‐effect studies have been carried out following intravenous injection of 10 mg metoclopramide hydrochloride to seven normal male volunteers. 2 It is proposed that a two‐compartment model adequately describes the disposition of the drug which is rapidly distributed (T1/2alpha = 4.9 +/‐ 1.1 min) and eliminated (T1/2beta = 165.7 +/‐ 20.2 min). Total body plasma clearance of the drug is high (10.9 +/‐ 1.5 ml min‐1 kg‐1) and approximates to liver plasma flow. 3 Metoclopramide i.v. increases gastric emptying as measured by an ethanol absorption test (P less than 0.005). The duration of this effect is at least 3 h. 4 Ethanol given after i.v. metoclopramide administration produces significant sedation during the first hour and at 3 h (P less than 0.001). 5 The effect of metoclopramide on gastric emptying, and the degree of sedation induced by ethanol would appear to be related to plasma metoclopramide concentration. 6 Metoclopramide increases serum prolactin to 59 +/‐ 5.8 microgram/1 at 30 min after injection. There is a linear relationship (r = 0.809) between serum prolactin increase and plasma metoclopramide concentration.
Human pancreatic growth hormone releasing factor ) is the parent molecule of several peptides recently extracted from pancreatic tumours associated with acromegaly. A study was conducted to examine its effects on the release of growth hormone in normal volunteers and in patients with hypopituitarism and acromegaly.GRF (1-44) dose dependently stimulated the release of growth hormone in normal people and produced no appreciable side effect. This response was grossly impaired in patients with hypopituitarism and, although similar to the growth hormone response to hypoglycaemia, was of quicker onset and a more sensitive test of residual growth hormone function. Patients with acromegaly appeared to fall into (a) those with a normal response to GRF, whose growth hormone suppressed significantly with oral glucose, and (b) those who had an exaggerated response to GRF (1-44), whose growth hormone had not suppressed previously after oral glucose.Present methods for testing growth hormone deficiency entail using the insulin stress test, which is time consuming, unpleasant, and sometimes dangerous. A single intravenous injection of GRF now offers the possibility of an easier, safer, and more reliable routine test for growth hormone deficiency. It has the further
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.