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 effects of oral bromocriptine in acromegaly have been studied. A dose of 5 mg six-hourly suppressed circulating growth hormone (GH) levels in nine out of 11 patients treated for seven to 11 weeks. This was associated with considerable clinical improvement in all patients, with abolition of excessive sweating, reduction in soft-tissue thichening, loosening of rings, decrease in shoe size, improvement in facial features, and loosening of dentures. Metabolic changes included improvement in glucose tolerance and reduction in hydroxyproline excretion. Unlike the actions of growth hormone release inhibiting hormone the suppression of GH was not accompanied by a reduction in insulin or glucagon secretion, though prolactin levels were suppressed. Side effects other than mild constipation were not seen when the full dose regimen was reached by slowly increasing the dose from 2-5 mg once daily. Bromocriptine holds promise as a safe and orally effective medical treatment to augment surgical or radiotherapeutic measures directed at the pituitary tumour. Its efficacy during longterm administration remains to be established.
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PMID:Bromocriptine treatment of acromegaly. 111 90

One mg of glucagon was given subcutaneously to eight patients with active acromegaly. Seven out of eight patients had a rapid decrease in serum growth hormone (GH) levels at 30 min after the glucagon injection. In two out of seven patients a rebound increase in serum GH following the early GH reduction was observed. On the other hand, oral administration of 50 g glucose which caused a comparable increase in blood glucose to that after the glucagon injection elicited no early suppression in serum GH levels in the same patients. These data suggest that the inhibition of GH release induced by glucagon could not be related to the increase in blood glucose by glucagon.
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PMID:Suppression of serum growth hormone levels by glucagon in patients with active acromegaly. 123 98

The acute suppressive effects of L-dopa and somatostatin (growth hormone release inhibiting hormone) on the elevated plasma GH concentrations of seven patients with acromegaly were compared. In addition the effects of the two agents on fasting concentrations of plasma glucose, insulin, glucagon and prolactin were studied. In six of the seven patients hourly samples for GH assay were taken from 08.00 to 20.00 hours on a control day. Synthetic cyclic somatostatin (100 mug) was infused intravenously in an albumin/saline solution over 75 min with a Harvard constant infusion pump. Levodopa 500 mg was given orally. Somatostatin infusion produced a reduction in plasma GH concentrations in six of seven patients (mean reduction 55%). L-Dopa produced a reduction in plasma GH concentrations in the same six patients (mean reduction 52%). The minimum GH concentrations achieved in the two tests were comparable and did not differ significantly from the minimum GH concentrations recorded during the 12 h control study. Mean plasma insulin and glucagon concentrations were also significantly reduced during the somatostatin infusion (P less than 0-025; P less than 0-05 respectively). Plasma glucose concentrations did not change. L-Dopa did not alter mean plasma glucose, insulin or glucagon values. Somatostatin did not alter prolactin values but L-Dopa suppressed basal values to less than 2 ng/ml in five patients. This study shows that the plasma GH change after the administration of L-dopa and somatostatin in acromegaly is comparable and confirms the pancreatic effects of somatostatin.
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PMID:A comparison of the effect of levodopa and somatostatin on the plasma levels of growth hormone, insulin, glucagon and prolactin in acromegaly. 126 63

A 42-year-old woman with a family history of multiple endocrine neoplasia type 1 (MEN 1) presented with symptomatic hypoglycaemia and peptic ulceration. Investigation revealed an insulinoma, hyperparathyroidism, hypercalcitoninaemia with a positive pentagastrin stimulation test, acromegaly due to a GRF-oma, hyperprolactinaemia and normal serum gastrin levels. Five pancreatic tumours were removed at laparotomy and immunostaining was positive for insulin, calcitonin, somatostatin and glucagon. Post-operatively she developed elevated serum gastrin levels and gross peptic ulceration, despite H2-blockers, and died of gastro-intestinal haemorrhage suggesting that removal of the somatostatinoma may have allowed increased gastrin secretion from a gastrinoma. This case emphasizes the importance of measuring a wide variety of tumour marker peptides in MEN 1 and suggests that caution is required in interpretation of the pentagastrin stimulation test in such cases. Patients with MEN 1 and known peptic ulceration may require perioperative omeprazole treatment even if serum gastrin levels are normal.
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PMID:A case of multiple endocrine neoplasia: hyperparathyroidism, insulinoma, GRF-oma, hypercalcitoninaemia and intractable peptic ulceration. 135 65

Although insulin-like growth factor I increases renal function, the renal haemodynamic abnormality underlying the glomerular hyperfiltration in acromegaly is unknown. In normal subjects, amino acids and low doses of dopamine increase the glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), presumably by a predominant vasodilation of the afferent and efferent glomerular arterioles, respectively. We studied baseline GFR and ERPF (determined with 125I-iothalamate and 131I-hippuran, respectively), the renal stimulatory effects of amino acid and dopamine infusion, and albuminuria before and after 3 months octreotide treatment in seven acromegalic patients with metabolically active disease. Octreotide reduced growth hormone concentrations from 14.7 +/- 3.0 to 5.5 +/- 1.0 micrograms l-1 (mean +/- SEM, n = 7; P less than 0.001) and insulin-like growth factor I levels from 4.12 +/- 1.31 to 2.44 +/- 0.68 kU l-1 (P less than 0.02). Glucagon concentrations did not change. Baseline GFR and ERPF declined from 132 +/- 5 to 117 +/- 6 and from 547 +/- 32 to 478 +/- 31 ml min-1 1.73 m-2, respectively (P less than 0.05 for both). Initially the response to amino acids was impaired (increment in GFR: 4.8 +/- 6.0%, NS; ERPF: -1.5 +/- 6.8%, NS), whereas the response to dopamine was normal (GFR: 10.6 +/- 1.1%, P less than 0.05: ERPF: 33.2 +/- 3.1%, P less than 0.01). After octreotide, amino acid infusion increased GFR by 15.0 +/- 6.8% (P less than 0.02) and ERPF by 11.3 +/- 5.6% (P less than 0.02), while the dopamine response was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of a somatostatin analogue, octreotide, on renal haemodynamics and albuminuria in acromegalic patients. 151 98

Side effects of octreotide may be local, biochemical, gastroenterological, or endocrinological. Local pain at the injection site occurs frequently, but rarely lasts more than 15 minutes and often resolves with continued therapy and may be improved if the vial is warmed prior to injection. No long-term hematological or biochemical abnormalities have been described. Despite initial diarrhea in some patients, no change in circulating fat-soluble vitamins has been consistently reported. Antibodies to octreotide have been described, but are rare. Abdominal pain or diarrhea can occur at the beginning of therapy. These symptoms rarely persist and are minimal if the injections are timed between meals, but this may increase the incidence of gallstones. Gallstones occur with increased frequency. Gastritis has been described as being an invariable consequence of long-term treatment with octreotide. We have found the incidence to be increased in patients on octreotide, but this is not invariable. Hypoglycemia may be exacerbated in some patients with insulinoma because of glucagon suppression. Small numbers of patients on octreotide for acromegaly have developed hypoglycemic. Conversely, carbohydrate tolerance may temporarily worsen because of insulin suppression and rarely oral hypoglycemia drug therapy may become necessary. Most frequently, carbohydrate tolerance does not deteriorate. In some patients with acromegaly, pituitary tumor size may continue to increase despite continued therapy. Last, there is the theoretical risk of addiction to a compound which may act through opiate receptors and considerably alleviates headache in some patients with pituitary tumor. Overall, despite the multiplicity of theoretical side effects, the majority of patients tolerate octreotide well, with no serious untoward effects.
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PMID:Proceedings of the discussion, "Tolerability and safety of Sandostatin". 151 39

The SRIF analog octreotide (SMS 201-995) has been in clinical use for over 6 yr in the treatment of acromegaly and metastatic endocrine pancreatic and carcinoid tumors. The use of the analog in the treatment of acromegaly and TSH-secreting tumors is beyond the scope of this clinical review. Patient acceptance of the analog, given chronically by the sc route, has been excellent and side effects have been few with the exception of the development of gallstones. In endocrine pancreatic and carcinoid tumors the hypersecretion of hormones such as VIP, glucagon, and gastrin and the secretory products of carcinoid tumors (e.g. 5-hydroxytryptamine and tachykinins) and their clinical effects may be successfully blocked. This allows excellent palliation of such tumors and often enables the patients to return home and lead normal social lives. Initial hopes that long-term octreotide therapy would be an effective antitumor drug, reducing tumor growth, based on experimental animal models and human tumor cell lines, have not been born out in clinical practice. A reduction in gut tumor bulk due to octreotide, rarely or never occurs as a sustained phenomenon. Eventually a decrease in, and finally an absence of, clinical effectiveness occurs despite the reintroduction of other treatment modalities.
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PMID:Clinical review 23: The use of the long-acting somatostatin analog octreotide in the treatment of gut neuroendocrine tumors. 164 13

A total of 79 consecutive patients with pituitary tumours were screened for multiple endocrine neoplasia type 1 (MEN-1). The 79 patients included 21 patients with acromegaly, nine with Cushing's disease, 18 with prolactinomas, three with mixed pituitary adenomas (GH and PRL), and 28 patients with no detectable hypersecretion of hormones. The screening consisted of: (1) a family history, (2) a uniform medical history of the patient using a standard questionnaire, and (3) hormonal evaluation including measurements of the serum levels of insulin, gastrin, glucagon, somatostatin, vasoactive intestinal polypeptide and pancreatic polypeptide. Ionized calcium and glucose concentration in serum were also measured. We found no patients with the MEN-1 syndrome. In one patient, we found a transient elevation of serum concentrations of pancreatic polypeptide for which we have no explanation. In another patient, the serum gastrin concentration was elevated secondary to achlorhydria. No other endocrine disorders were found, and no patients had relatives with recognized endocrine pancreatic tumours, primary hyperparathyroidism (HPT), or pituitary adenomas.
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PMID:Screening for multiple endocrine neoplasia type 1 in patients with recognized pituitary adenoma. 198 64

Octreotide is a long-acting cyclic octapeptide with pharmacologic actions mimicking those of the natural hormone somatostatin. It can suppress the secretion of serotonin, as well as the gastroenteropancreatic peptides gastrin, vasoactive intestinal peptide (VIP), insulin, glucagon, secretin, motilin, and pancreatic polypeptide. It also suppresses growth hormone and decreases splanchnic blood flow. Octreotide is completely and rapidly absorbed following subcutaneous injection and has an elimination half-life of 1.5 hours. Clinical trials reviewed here show octreotide useful in the treatment of diarrhea associated with VIP secreting tumors, as well as diarrhea and flushing associated with carcinoid syndrome, both conditions for which the drug is approved. Clinical trials involving the use of octreotide in the treatment of acromegaly are also reviewed. Adverse reactions to octreotide are mild to moderate and most commonly involve injection site pain and diarrhea. Drug interactions are apparently related to the drug's pharmacologic effects. Octreotide is given subcutaneously two to three times daily, with daily doses ranging from 50mcg to 1,500mcg per day. Further research appears necessary to clarify dosing issues.
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PMID:Debut of a somatostatin analog: octreotide in review. 255 39

The chemistry, pharmacology, pharmacokinetics, clinical uses, adverse effects and drug interactions, dosage, availability and cost, and indications for use of octreotide, a new synthetic analogue of the peptide hormone somatostatin (SS), are reviewed. Like SS, octreotide suppresses secretion of pituitary growth hormone (GH) and thyrotropin and decreases release of a variety of pancreatic islet cell hormones including insulin, glucagon, and vasoactive intestinal peptide (VIP). Octreotide also reduces splanchnic blood flow, gastric acid secretion, GI motility, and pancreatic exocrine function and alters the absorption of water, electrolytes, and nutrients from the GI tract. The elimination half-life of i.v. octreotide is 72-98 minutes, compared with 2-3 minutes for i.v. SS. Usual administration of octreotide is by the i.v. or s.c. route. Octreotide has been studied in the treatment of hormone-secreting pituitary tumors and pancreatic islet cell tumors. Octreotide therapy lowers GH secretion and improves clinical symptoms in patients with acromegaly and may suppress clinical symptoms to a greater degree than bromocriptine. Patients with carcinoid syndrome and VIP-secreting tumors (vipomas) have had substantial improvement in clinical symptoms with administration of octreotide. This agent does not appear to be effective in the treatment of nonvariceal upper GI bleeding and acute pancreatitis; its relative usefulness in the treatment of variceal bleeding is not established. Adverse effects associated with octreotide therapy generally have been mild, including pain or burning at the injection site, abdominal pain, and diarrhea. Octreotide has been shown to interfere with absorption of oral cyclosporine. Standard initial therapy is octreotide acetate 50-100 micrograms s.c. every 8-12 hours, with titration based on clinical and biochemical effects. Up to 3000 micrograms/day of octreotide acetate has been administered to patients with acromegaly without serious adverse effect. Octreotide is marketed under the brand name Sandostatin and is available in 1-mL ampuls containing 50, 100, and 500 micrograms of octreotide acetate. Because the conditions for which octreotide appears to be most effective are uncommon, the drug should be considered for addition to the formulary in tertiary-care institutions only; addition of octreotide to the formulary of a community hospital is probably unnecessary. The synthetic analogue octreotide is longer acting and more specific in pharmacologic action than SS.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Octreotide, a new somatostatin analogue. 265 11


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