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)

Tests were performed of the effects of the Somatostatin (SMS) upon the concentration of Insulin, Glucagon and STH, as well as of the effects of SMS upon the specific binding of the insulin to the receptors. The tests were carried out on eight insulin-independent diabetics, and five healthy volunteers. The tests were made with placebo, followed by 100 ug of the analogue SMS 201-995, known under the name of Sandostatin. Blood specimens for determining all parameters mentioned above were taken at 9 a.m., 3 p.m., 9 p.m., and 3 a.m. (09 h, 15 h, 21, and 03 h). The goal of the tests was to determine whether the SMS had any effect upon the glucoregulation, and at which level changes take place. In the group of healthy volunteers, a considerable decrease of insulin took place six hours after the administration of STH, and the decrease of the glucagon was especially marked, tending to increase again after six hours, while the specific binding of the insulin to the receptors, and the number of receptors were decreased six hours following the administration of the SMS when compared with the placebo, and without tending to reach the previous levels until 3 a.m. (03 h). In insulin-independent diabetics, the SMS leads to a considerable drop of concentrations of Insulin, Glucagon, STH and to a specific binding of the insulin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The effect of somatostatin on specific binding of insulin to receptors in patients with non-insulin dependent diabetes]. 168 Jul 75

A 69-year-old woman with classic glucagonoma syndrome had associated progressive neurologic disease manifest as dementia, ataxia, optic atrophy, and lower limb weakness. Visual evoked responses (VERs) were absent bilaterally. After an attempt at resection was unsuccessful, therapy was started with somatostatin analogue (Sandostatin, SMS 201-995). Over the ensuing 3 months, there was a decrease in the plasma glucagon level, resolution of the rash, weight gain, reversal of the dementia, and an improvement in coordination and limb weakness. Subsequent VERs revealed bilateral delayed responses.
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PMID:Reversal of a neurologic paraneoplastic syndrome with octreotide (Sandostatin) in a patient with glucagonoma. 195 89

Octreotide (Sandostatin), a potent and long-acting octapeptide analogue of somatostatin, exhibits variable metabolic effects in type 1 diabetes. We have postulated that interindividual variability in octreotide metabolism could be responsible in part for the differences in metabolic responses reported in previous clinical studies. To this end, we determined plasma levels and MCR of octreotide during 24-hour continuous SC infusion (low dose, 200 micrograms; high dose, 400 micrograms) in nine female, C peptide-negative patients with type 1 diabetes. The metabolic effects of the analogue were assessed by measuring serum glucose, free insulin, glucagon, GH, and PP levels before and at 1- to 2-hour intervals during each dose of the analogue or control (0.9% saline solution) infusion in a single-blind randomized manner. Mean daytime (0800-0000 hours) and bedtime (0000-0800 hours) serum glucose levels decreased significantly (p less than 0.05 to 0.02) during analogue therapy compared with control. Mean serum free insulin levels were significantly (p less than 0.02) greater during octreotide infusion compared with control, despite the similar daily insulin requirements. Both doses of the analogue effectively suppressed 24-hour GH by 50%, glucagon by 50%, and PP by 80%. Steady-state octreotide levels varied considerably among patients (low, mean +/- SEM), 1000 +/- 101, range 638 to 1375 pg/ml; high, mean 1940 +/- 147, range 1032 to 2462 pg/ml). Although mean MCR values were similar with both doses, we observed greater interindividual variability (low, mean 2.45 +/- 0.30, range 1.31 to 3.78 ml/kg/min; high, mean 2.36 +/- 0.19, range 1.68 to 3.48 ml/kg/min).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Continuous subcutaneous octreotide infusion: dose-response relationships between metabolic effects and octreotide clearance in patients with insulin-dependent (type 1) diabetes. 206 44

The clinical presentation of Zollinger-Ellison syndrome (ZES) is the result of gastrin hypersecretion and may be modified by secondary peptide hypersecretion. Treatment is medical (H2-blockers) or surgical (tumor excision and total gastrectomy). H2-blocker escape occurs up to 23 per cent and surgical mortality ranges to 15 per cent. Treatment of advanced disease has limited success. Sandostatin (SMS 201-995) has been shown to decrease basal gastrin and gastric acid secretion in ZES. We hypothesized that SMS would suppress basal and provoked gastrin and secondary peptide secretion in ZES. A patient with refractory, metastatic gastrinoma underwent provocative testing (test meal, calcium infusion, secretion bolus and tolbutamide bolus). Thirteen peptides were drawn at set intervals during these provocative tests. Testing was repeated during SMS therapy (100 micrograms subcutaneously three times per day). Gastrin, pancreatic polypeptide (PP) and glucagon levels were elevated at baseline. SMS suppressed all three peptides (mean 74 per cent) (p less than 0.05). Gastrin, PP and glucagon were provoked by all four tests (means above baseline, 19, 155 and 138 per cent, respectively). Gastrin-releasing peptide, gastric inhibitory peptide and insulin were provoked by calcium infusion (427, 306 and 162 per cent above baseline, respectively). SMS suppressed 14 of 15 of these peaked-provoked peptide levels (mean 72.5 per cent, p less than 0.05). Gastric analysis during calcium infusion showed SMS suppression of hourly gastric secretory volume by 77.5 per cent and of acid production (milliequivalents of acid) by 87.5 per cent. During a 20 month follow-up period, the patient was maintained on SMS, 200 micrograms subcutaneously three times per day. She has remained asymptomatic. Interval peptide profiles at two, eight and 18 months show normal gastrin, PP and glucagon levels. A computed tomographic scan at eight months shows a remarkable regression of primary and metastatic tumor. Regrowth, however, was noted at 19 months. SMS may be useful in ZES by suppressing basal and provoked gastrin and secondary peptide secretion and may occasionally give palliation by yielding temporary tumor registration.
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PMID:Effect of somatostatin analog on peptide release and tumor growth in the Zollinger-Ellison syndrome. 218 84

The long acting somatostatin analogue octreotide acetate has been effective in the treatment of early dumping syndrome. We hypothesized that this may be related to its effects on inhibiting gastric emptying and delaying intestinal transit. To study the effect of octreotide acetate on intestinal motility in patients we carried out a randomized, double-blinded study using a subcutaneous injection of either octreotide acetate (100 micrograms) or placebo given 20 min prior to ingestion of a high carbohydrate "dumping" meal in six patients with known severe dumping syndrome. Prior to each study a multilumen polyethylene tube was inserted into the efferent limb to study small intestinal contractions using low compliance pneumo-hydraulic water-perfused manometry. Octreotide acetate prevented dumping symptoms in all six patients and induced the appearance of migrating myoelectric complexes (MMC) characteristic of interdigestive motility. After ingestion of the dumping meal the postprandial "fed" motility pattern lasted for 141 +/- 9 min while after octreotide acetate the fed motility lasted for 29 +/- 5 min (P less than 0.03). The vigor of the fed motility pattern as measured by the motility index (MI = loge (sum of amplitudes X No. of contractions + 1] was lower after octreotide acetate than after placebo (15.1 +/- 0.1 vs 13.4 +/- 0.2, P less than 0.03). The induction of fasting MMC motility pattern and reduction in the duration and vigor of fed motility may explain the symptomatic relief these patients obtained with octreotide acetate. It is not known whether the induction of the MMC is a direct effect of octreotide acetate or secondary to the concomitant inhibition of peptide release (neurotensin, insulin, glucagon, pancreatic polypeptide) that has been demonstrated in earlier studies.
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PMID:Octreotide acetate induces fasting small bowel motility in patients with dumping syndrome. 226 84

Adult onset nesidioblastosis (AON) is an extremely rare entity associated with hypersecretion of insulin. Previous reports have demonstrated that the somatostatin analog, Sandostatin (SMS), will control the clinical symptoms induced by infantile nesidioblastosis. We hypothesized that insulin, C-peptide, and secondary peptide secretion from AON is provocable. We also hypothesized that SMS would suppress both basal and provoked primary and secondary peptide secretion in AON. To test this hypothesis, in a patient with AON, 13 gut peptide levels were determined at set intervals during provocative testing with a test meal, a calcium infusion, a secretin bolus, and a glucagon bolus. These tests were repeated under the influence of SMS. Insulin, C-peptide, and pancreatic polypeptide (PP) levels were elevated in the basal state. SMS suppressed all three peptides (mean 68%) (p less than 0.05). Basal fasting glucose rose by 65%, and glucose ratios were raised throughout all four tests. Insulin:glucose ratios decreased during SMS therapy. Insulin and PP secretion was increased by all four provocative tests (mean 458% and 665% above baseline, respectively). C-peptide was provoked by three tests (mean 204%). Peptides with normal basal values were also provocable. GRP and glucagon were provoked by secretin stimulation (182%, 186%, respectively). Calcium infusion stimulated CIP release by 372%. SMS suppressed the peak provoked peptide levels in all positive provocation tests (p less than 0.05). Peak provoked insulin values were decreased by 59%, C-peptide by 75%, and PP by 92%. Peak provoked glucagon, CRP, neurotensin, and GIP levels were decreased by 20%, 65%, 51%, and 73%, respectively. The patient has been maintained on SMS (25 micrograms bid) for 1 yr and has shown decreased insulin levels, normal glucose levels, and, at 1 yr, leads an asymptomatic normal life. SMS is able to suppress primary and secondary peptide secretion in both the fasting and provoked state. The long-term efficacy of SMS may be predicted by its ability to suppress primary peptide release during peak provocation.
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PMID:Adult onset nesidioblastosis: response of glucose, insulin, and secondary peptides to therapy with Sandostatin. 240 44

Sandostatin (SMS 201-995 (SMS)), a potent, long acting analog of native somatostatin was used in five patients with functional endocrine tumors (gastrinoma, two patients; insulinoma, one patient; glucagonoma, one, and adult onset nesidioblastosis, one). Primary and secondary peptide levels were obtained during provocation with a test meal, a calcium infusion, a secretin bolus and either a glucagon or tolbutamide bolus. During provocation test, the levels of the primary peptides insulin and C-peptide (nesidioblastosis and insulinoma), gastrin (gastrinoma), glucagon (glucagonoma) and the secondary peptides calcitonin, gastrointestinal peptide, gastrin releasing peptide, motilin, neurotensin, pancreatic polypeptide, somatostatin, substance-P and vasoactive intestinal peptide were obtained at predetermined intervals and quantitated by radioimmunoassay. SMS therapy was begun and peptide levels were again obtained during provocation. SMS suppressed basal primary peptide levels in all patients by more than 50 per cent. In 23 of 26 provocative tests, SMS effectively decreased circulating peptide levels by more than 50 per cent. Thirteen instances of elevated basal secondary peptides were discovered, and SMS universally suppressed these levels by a mean of 54 per cent. Of the 44 provocative tests performed, elevated secondary peptide levels were present in 41. SMS was effective in 31 of these 41 tests. The mean suppression of these provoked secondary peptide levels was 70 per cent. SMS effectively suppresses both basal and provoked peptides and, thus, provides relief of the clinical symptoms induced by pathologic elevations of primary and secondary peptides.
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PMID:Suppression of primary and secondary peptides with somatostatin analog in the therapy of functional endocrine tumors. 246 Sep 58

Recently somatostatin analogues were successfully used to control insulin-induced hypoglycemia in patients with insulinoma. We observed a transient decrease in glucose levels and symptomatic hypoglycemia after administration of the long-acting somatostatin-analogue octreotide (Sandostatin) in two insulinoma patients. We studied the acute effects of octreotide (administered before breakfast) on blood glucose and gluco-regulatory hormones in these patients. In one patient, we studied the effects of glucagon replacement and changing the time of breakfast (relative to octreotide administration) on octreotide-associated changes in blood glucose and glucoregulatory hormones. Compared with control levels, octreotide therapy reduced insulin levels. During hypoglycemia glucagon and growth hormone levels were suppressed, but cortisol levels appropriately increased. The increase in catecholamine levels was normal in one patient, but markedly attenuated in the other. A transient decrease in serum glucose after octreotide was absent after glucagon replacement, but present when breakfast was taken before administration of octreotide. We conclude that in patients with insulinoma, octreotide therapy may be associated with clinically important hypoglycemia, during which counterregulatory hormone secretion may be attenuated.
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PMID:Aggravation of hypoglycemia in insulinoma patients by the long-acting somatostatin analogue octreotide (Sandostatin). 254 62

The potential use of somatostatin-14 and its long lasting analogue Sandostatin as antiulcer agents led us to study the functional properties of these peptides on the histamine H2-receptor H2R adenylate cyclase system in gastric glands isolated from the rat fundus. The action of the two peptides has also been compared on membrane receptors sensitive to isoproterenol and the truncated glucagon-like peptide TGLP-1. The data indicate that somatostatins inhibit selectively H2R and TGLP-1 receptor activity with similar potencies and kinetics, suggesting that the two peptides share the same receptor pool coupled with the Gi subunits of adenylate cyclase. Somatostatin-14 and Sandostatin have no evident action on the beta 2-type adrenergic receptor beta 2R. Therefore, the higher potency of Sandostatin compared to somatostatin-14 in inhibiting acid secretion is probably related to an increased stability of the analogue in vivo.
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PMID:Differential regulation of membrane receptors sensitive to histamine (H2-type), isoproterenol (beta 2-type) and glucagon-like peptides by the somatostatin analogue Sandostatin in rat gastric glands. 256 37

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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