Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The response of growth hormone, cortisol, and catecholamines to hypoglycaemia produced by a continuous intravenous infusion of insulin was investigated in 10 normal subjects and 15 patients with pituitary disease. The insulin infusion rate was started at 2 U/hour for adolescents, 4 U/hour for adults, and 6 U/hour for patients with acromegaly. If required the rate was increased during the test depending on changes in blood glucose, measured by a Reflomat with low reading glucose oxidase strips. Stopping the infusion when the blood glucose concentration had fallen to 2.0 mmol/l (36 mg/100 ml) resulted in a maximum further fall of 0.7 mmol/l (13 mg/100 ml) and a subsequent spontaneous rise in blood glucose concentration. The rise was identical in normal subjects and in patients with hypopituitarism, further evidence that pituitary hormones--in contrast to glucagon and catecholamines--are relatively unimportant in the recovery from hypoglycaemia. The only patient who required intravenous glucose to restore normoglycaemia was a patient with longstanding insulin dependent diabetes. A comparison with the conventional bolus injection test showed that continuous intravenous insulin infusion was more reliable in producing adequate but not excessive hypoglycaemia and the hormone responses were equivalent. The continuous intravenous insulin infusion may offer particular advantages in the investigation of growth hormone deficiency.
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PMID:Testing the anterior pituitary: hypoglycaemia produced by continuous intravenous insulin infusion. 641 Dec 30

We report the histological, ultrastructural, and immunocytochemical features of six hypothalamic gangliocytomas associated with pituitary GH cell adenomas and/or acromegaly. In four patients, the gangliocytoma was intrasellar, and no hypothalamic investigation was performed; in two patients, autopsy confirmed hypothalamic involvement. Four patients had a gangliocytoma associated with pituitary GH cell adenoma and acromegaly; electron microscopy demonstrated an intimate association between neurons and adenomatous GH cells. One patient had a gangliocytoma and a GH cell adenoma but no clinical evidence of acromegaly. In the sixth patient, clinical and biochemical acromegaly was manifest, but no pituitary adenoma was demonstrated. Using immunocytochemistry, human pancreatic tumor GRF (hptGRF-40) was localized in the majority of neurons of all six gangliocytomas. The pituitary adenomas and nontumorous adenohypophyses were negative for hptGRF-40. In addition, somatostatin, glucagon, and GnRH were demonstrated within some neurons of several tumors; insulin and gastrin stains were equivocal. These findings confirm previous proposals of production of a GRF by such gangliocytomas. While the significance of other peptides found in some of the tumors is uncertain, the presence of hptGRF-40 in neurons of these gangliocytomas supports the theory that GRF excess is the mechanism responsible for over-production of GH and provides evidence for a syndrome of hypothalamic acromegaly.
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PMID:A case for hypothalamic acromegaly: a clinicopathological study of six patients with hypothalamic gangliocytomas producing growth hormone-releasing factor. 642 59

In exceptional cases, acromegaly develops as the clinical expression of an ectopic secretion of Growth Hormone (GH) or Growth Hormone-Releasing Factor (GRF), tumorous in origin. In the present report, we describe an instance of acromegaly caused by the secretion of GRF from a voluminous pancreatic tumor. The resection of this tumor resulted in a temporary disappearance of the biological and clinical symptoms of acromegaly, which then reappeared in conjunction with a rise in plasma GRF. From this pancreatic tumor, substances displaying a potent GRF activity were isolated and characterized. Amino acid analyses revealed that they were related to 3 peptides containing respectively 44, 40 and 37 aminoacids. The largest (hp GRF (1-44)-NH2) referred as hp GRF or somatocrinin is considered to be the primary molecule. The pancreatic tumor was multisecreting as proved by high plasma levels of somatostatin, pancreatic polypeptide and glucagon, normalized after the tumor removal, taken together with the immunocytochemical demonstration of the presence of these peptides in the tissue and with the isolation of somatostatin. In contrast hypercalcemia associated with an elevated plasma level of IR-PTH was unmodified by tumor removal. Diagnosis of acromegaly as ectopic endocrine syndrome will probably be facilitated by plasma GRF radioimmunoassay, as a result of production of anti synthetic GRF antibodies.
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PMID:[Acromegaly, clinical expression of the production of growth hormone releasing factor in pancreatic tumors]. 643 Feb 7

This report describes the histologic, immunocytochemical, and ultrastructural study of a multihormonal carcinoid tumor of the pancreas, secreting a growth hormone releasing factor (GRF) which provoked acromegaly. The patient presented a nonfamilial multiple endocrine neoplasia, type 1. The absence of radiologic signs of a pituitary adenoma in conjunction with elevated plasma levels of pancreatic polypeptide, glucagon, somatostatin, as well as growth hormone (GH), led to the discovery of the tumor. Its surgical excision produced a rapid disappearance of most of the clinical and biologic disorders. No immunoreactive GH was found in the tumor using radioimmunoassay and immunocytochemistry. In contrast, three peptides with GH-releasing activity were extracted and characterized. Immunocytochemistry showed that the GRF-reactive cells, together with rare somatostatin-storing cells, made up areas which demonstrated a medullary pattern of growth with extracellular amyloid deposits. Under electron microscopic examination, actively secreting cells were observed which carried endocrine granules of 100 to 150 nm in diameter. The other regions of the tumor presented a different type of growth and were composed of pancreatic polypeptide-, glucagon-, or somatostatin-reacting cells. Cells immunostained with antisera raised against beta-endorphin were also noted. These data suggest that GRF may be a new biologic marker for pancreatic endocrine tumors.
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PMID:Multihormonal carcinoid tumor of the pancreas. Secreting growth hormone-releasing factor as a cause of acromegaly. 643 52

[Phe4]Somatostatin was twice as active as somatostatin (SS) in suppressing rat growth hormone release in vitro but had only weak activity toward inhibition of insulin and glucagon release in vivo. The ability of this analogue to inhibit growth hormone release more actively than SS was confirmed in vivo by two separately designed bioassays. Further structure/activity studies of position 4 were carried out with [Glu4]SS, [Thr4]SS, and des-Lys4-SS, all of which had negligible inhibiting activity in the pituitary and pancreas. In this context the strikingly selective activity of [Phe4]SS suggests a fundamental difference in the SS receptors of pituitary and pancreas and the normal side-chain basicity of position 4 appears to be more important for action in pancreas than in pituitary. [Phe4]SS has properties that may be useful in the development of agents for the treatment of acromegaly or other disorders associated with increased growth hormone levels.
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PMID:[Phe4]somatostatin: a potent, selective inhibitor of growth hormone release. 698 57

Sixteen patients with clinically active acromegaly were investigated; four of these had insulin-independent diabetes mellitus. Those acromegalic subjects who were not diabetic exhibited excessive insulin responses to glucose and arginine stimulation. By contrast, plasma glucagon concentrations in these patients did not differ significantly from those in control subjects. Acromegalic patients who also had insulin-independent diabetes had a markedly reduced insulin response to glucose stimulation, while arginine-induced insulin secretion was relatively well preserved. Although there was a tendency for plasma glucagon concentrations to be higher in the diabetic than in the nondiabetic group of acromegalic subjects, this difference did not achieve statistical significance either in the basal state or during the glucose amd arginine infusion tests.
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PMID:Plasma glucagon and insulin concentrations in acromegaly. 699 31

Acromegaly is very often accompanied by impaired glucose tolerance or a manifest diabetes mellitus, with increased immunoreactive insulin (IRI) levels whose response during oral glucose tolerance tests (OGTT) is quite often exaggerated. When the dopaminergic drug bromocriptine is administered to acromegalics, their elevated growth hormone (GH) levels very often decrease, their impaired glucose tolerance (as manifested in OGTT) improves and their exaggerated IRI response becomes more normal. Eighteen patients were treated with bromocriptine. They were followed-up repeatedly during their treatment of varying duration for up to 6 years. These results indicate that raised GH levels are not the only factor that impairs glucose tolerance in acromegalics. During bromocriptine administration, impaired glucose tolerance improved and abnormal IRI levels (OGTT) became more normal even without any decrease in the high GH levels. In non-diabetic acromegalics, when bromocriptine was administered, there was not only an average decrease in the elevated GH values during OGTT, but a normalization of increased IRI values as well, without any major change in the corresponding blood glucose levels. During insulin tolerance tests (ITT), after i.v. insulin, the IRI levels after 30 and 60 min were markedly higher in acromegalics on bromocriptine than in the same patients before its administration, without any significant change in the corresponding blood glucose values. In 2 diabetic acromegalics, bromocriptine administration re-established their lost ability to increase IRI levels during OGTT. This was accompanied by a marked improvement in their glucose tolerance. It is probable that bromocriptine decreases glucagon levels in acromegalics, or at least in some of them. It is suggested that bromocriptine could protect the beta-cells of acromegalics from "exhaustion'.
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PMID:Bromocriptine and glucose tolerance in acromegalics. 704 36

The effects of glucagon on the adrenergic system have been studied in experimental and clinical conditions. 1. in vitro studies: In the first experiment a continuous flow incubation system was developed in which the secretory response to these drugs was characterized by a serial fluorimetric assay of catecholamines in the effluent medium. Pig adrenal medulla or human pheochromocytoma were studied. There was an initial massive release of catecholamines which declined to basal levels (0.02 micrograms/mg) after 1.5 hours. When 10(-4) glucagon was infused for 10 minutes following 2 hours of preincubation, both adrenaline and nonadrenaline outputs rose abruptly to concentrations of 0.08 micrograms/mg and 0.07 micrograms/mg respectively. In the second experiment the effect of these drugs on the in vitro release of catecholamines from the isolated in vitro chromaffin granules of the pig adrenal medulla were studied. The results were the same as in the previous experiment. 2. clinical studies: The effects of glucagon were studied on the blood pressure and urinary catecholamine levels of healthy control subjects, of patients suffering from essential hypertension, thyroid disease, diabetes mellitus and acromegaly. Glucagon induced a slight but constant increase in blood pressure. By contrast no significant urinary catecholaline elevation was evoked. There was no difference in the effect of intravenous glucagon between normal subjects and patients suffering from the above-mentioned disorders.
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PMID:[A reevaluation of the glucagon provocative test for pheochromocytoma--on the in vitro release of catecholamine from the adrenal medulla or pheochromocytoma tissue, and on the effect of intravenous glucagon on urinary catecholamine excretion and blood pressure (author's transl)]. 740 74

Octreotide is a synthetic octapeptide somatostatin analogue which has higher potency and longer duration of action than the natural hormone. It is effective after subcutaneous administration and no rebound hypersecretion has been observed. Pharmacological effects of octreotide include inhibition of numerous hormones (growth hormone, TSH, insulin, glucagon and all gut hormones), of exocrine secretion (gastric acid, pancreatic enzyme), and of small-bowel absorption. This review deals with clinical application of octreotide in endocrine disorder. In patients with acromegaly octreotide treatment results in decrease of growth hormone (GH) and IGF-I together with tumour shrinkage and clinical improvement. Although variability in response to treatment is obvious for majority of patients the most effective dose is 100 mcg three times daily subcutaneously. Normalization of GH levels could be achieved in more than 50% of treated patients. It has also been shown that octreotide could be effective in TSH secreting pituitary adenoma, ACTH secreting adenoma as well as in non-secretory pituitary tumours. A marked biochemical and clinical responses together with longer survival have been reported in most of the patients with gastroenteropancreatic (GEP) tumours. Patients who benefit the most from octreotide therapy are those with carcionid syndrome (successful control of diarrhoea, flushing episodes and wheezing) and VIPomas (control of diarrhoea). In patients with insulin-dependent diabetes mellitus (IDDM) octreotide suppresses GH levels, postprandial blood glucose increases with resultant decrease in daily insulin requirements. In women with polycystic ovary syndrome (PCOS) octreotide has inhibitory effect on serum LH and ovarian androgens. This could have beneficial effect on ovulatory performance in women with PCOS.
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PMID:[Clinical use of octreotide (Sandostatin) in endocrinology]. 799 11

A number of endocrine disorders are associated with varying degrees of glucose intolerance. Sustained hypersecretion of hormones with actions antagonistic to insulin (e.g., GH, glucocorticoidos, catecholamines, glucagon) or which interfere with insulin secretion (e.g., catecholamines, hypokalemia) is often associated. And so, acromegaly, Cushing's syndrome, pheochromocytoma, primary aldosteronism, hyperthyroidism, glucagonoma and others are included in endocrine-associated diabetes. The glucose intolerance occurring secondary to endocrine disorders is usually moderate degree and overt diabetes with symptomatic hyperglycemia is an uncommon event, unless an underlying genetic diabetic diathesis also present in the same individual. The small subgroup of acromegalics(5-10%) with severe glucose intolerance requiring insulin therapy have low endogenous insulin levels and insulin responses that are markedly impaired. It has been suggested that these patients are really true diabetics. These are patients with NIDDM. Retinal, renal and neurological complications are uncommon in patients with endocrine-associated diabetes.
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PMID:[Diabetes secondary to endocrinolopathies]. 891 32


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