Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Growth hormone (GH) hypersecretion is well documented in insulin-dependent diabetes mellitus (IDDM). Somatostatin inhibits GH in acromegalics and healthy subjects although data on its inhibitory effects on high GH levels in IDDM patients are controversial. The effect of treatment with the somatostatin analogue octreotide ("Sandostatin") on GH secretion, IGF1 levels and metabolic control was investigated in insulin-dependent diabetics. Growth hormone and blood glucose were measured at hourly intervals whilst IGF-I was measured every 6 hours during the 24-h period before and after 7 days' treatment with octreotide (200 micrograms subcutaneously three times daily) in 10 C-peptide negative diabetics. Octreotide significantly reduced mean 24 h GH profile (7.2 +/- 0.7 mU/L before; 5.2 +/- 0.5 mU/L on octreotide, p less than 0.01), IGF-I levels (0.62 +/- 0.06 before; 0.47 +/- 0.05 on octreotide, p less than 0.005) mean 24 h blood glucose (14.4 +/- 0.5 mmol/L before; 12.6 +/- 0.4 mmol/L on octreotide, p less than 0.001) and daily insulin requirements (44.8 +/- 3.0 IU before; 37.2 +/- 3.0 IU on octreotide, p less than 0.02). The shape of 24 h GH profile curve changed significantly on octreotide treatment (p less than 0.05) when it consisted of three nadirs and three peaks closely linked with the time of octreotide administration. Moderate (abdominal discomfort) to severe hypoglycaemia) transient side effects have been observed in all treated patients. The results of this study showed that short-term treatment with octreotide given s. c. every eight hours modulates the pattern of GH secretion in C-peptide negative insulin-dependent patients.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The effect of the somatostatin analogue octreotide on growth hormone secretion in insulin-dependent diabetics without residual insulin secretion. 151 89

Carbohydrate tolerance and serum lipids were studied in 14 patients with acromegaly before and in response to treatment with high dose somatostatin analogue (octreotide) over a 14-week period. Patients were assessed with respect to growth hormone (GH) profile, IGF1, HbA1, fasting lipids, and the GH, glucose, and insulin response to a standard 75 g oral glucose tolerance test (OGTT) before and during therapy. Prior to treatment mean fasting serum insulin levels were 11.7 +/- 2.8 (+/- SE) mU I-1 with a mean insulin response to OGTT of 49.8 +/- 10.8 mU I-1. Twelve of the 14 patients responded to octreotide with a reduction in mean 24-h serum GH (32.9 +/- 9.3 to 4.3 +/- 0.9 mU I-1), suppression of GH at 60 min during OGTT (3.0 +/- 0.8 mU I-1) and normalization of serum IGF1 (71 +/- 7 to 27 +/- 3 (normal 9-48 nmol I-1)). In this group the fasting insulin levels fell to 2.2 +/- 0.7 mU I-1 (p less than 0.01), and mean insulin response during OGTT was reduced (46.6 +/- 15.0 to 12.3 +/- 2.3 mU I-1) (p less than 0.01). Despite the reduction in insulin secretion there was no significant deterioration in fasting blood glucose (4.8 +/- 0.2 vs 4.6 +/- 0.4 mmol I-1), HbA1 (7.2 +/- 0.3 vs 6.8 +/- 0.3%) or mean blood glucose response to OGTT (7.9 +/- 0.7 vs 8.2 +/- 0.5 mmol I-1). Fasting triglycerides were reduced with treatment from 1.5 +/- 0.2 to 1.1 +/- 0.1 mmol I-1 (p = 0.04) in the responsive group, but serum cholesterol levels were not significantly altered (5.3 +/- 0.3 vs 5.2 +/- 0.3 mmol I-1).
 ...
PMID:Carbohydrate tolerance and serum lipids in acromegaly before and during treatment with high dose octreotide. 183 50

To appreciate the IGF1 sensitivity of breast tumors we detected IGF1-R with a biochemical assay (RRA). We then localized and quantified IGF1-R on frozen tissue sections by histo-autoradiographic analysis (HAA). In some cases, the IGF1 and IGF1-R mRNA expression were studied by Northern blot analysis. We also studied the IGF1 plasma concentration in primary breast cancers compared to controls. IGF1-R (RRA) were found in 87% (n = 297) of the breast cancers. The mean geometric value was 3.87% (specific binding as percentage of total radioactivity); we found a highly significant correlation between IGF1-R and ER on the one hand (P = 0.0001) and PgR on the other (P = 0.0001) (Spearman test). The presence of IGF1-R was associated with a better prognosis, either on relapse-free survival (actuarial analysis: P = 0.004; Cox analysis: P = 0.005) or overall survival (respectively P = 0.003; P = 0.005). The median duration of follow-up was 30 months. By Cox analysis IGF1-R was a better prognostic factor than ER and PgR. In a series of 77 cases of benign breast disease only 47% (36/77) were positive; the mean geometric level was 1.8%. The HAA IGF1-R quantification in 20 breast carcinomas and 12 cases of benign breast disease confirmed the RRA results and demonstrated that the labeling was localized on the epithelial component. In four breast cancers, we did not detect IGF1 mRNA; IGF1-R probe demonstrated two major mRNAs of 11 and 7 kB. Finally we found that IGF1 plasma level was higher in breast cancer patients than in healthy controls of the same age. These results show that IGF1 is implicated in breast cancer growth and suggest that anti-IGF1 treatment might be useful in human breast cancer: for this reason, we and others carried out a phase II clinical trial with somatostatin.
 ...
PMID:Insulin-like growth factor 1 receptors (IGF1-R) and IGF1 in human breast tumors. 217 65

Plasma somatostatin (SRIF), growth hormone (GH), somatomedin C (IGF1), osteocalcin (BGP), 1,25-dihydroxyvitamin D (1,25-(OH)2D), calcium and inorganic phosphorus were measured in 10 chronically-catheterized fetal calves and in their dams during the two last months of gestation. Thus fetal life is associated with high levels of GH (1.53 +/- 0.14 nmol.l-1), BGP (64 +/- 4 nmol), Ca (2.90 +/- 0.06 nmol.l-1) compared to the results obtained in the pregnant cows. The first week of postnatal life was associated with a tremendous increase in plasma SRIF concentration (from 36 +/- 5 to 106 +/- 15 pmol.l-1; P less than 0.01). These results agree with an intense bone growth during the end of fetal life in the bovine species. However, IG 1 might not play a major role in the regulation of fetal skeletal growth during this period.
 ...
PMID:Systemic bone growth factors concentrations in calves during the perinatal period. 290 75

Octreotide, the first somatostatin analogue developed, has pharmacological properties (it inhibits pituitary GH and TSH secretion, pancreatic and digestive tract endocrine secretion and various gastrointestinal functions) which are qualitatively similar to those of the natural 14 amino acids peptide. Enzymatic structural modification had resulted in a peptide which is very resistant to degradation and has a 90-110 min half-life permitting subcutaneous administration. Following a subcutaneous injection of 50 to 100 micrograms, absorption is rapid and complete. The peak plasma concentration is obtained within 20 to 30 minutes. The drug is degraded mostly in the liver. Among pituitary tumours, GH- and TSH-secreting adenomas constitute the primary indication. Octreotide has been widely tested in the treatment of acromegaly; 50 to 80 percent of patients with that disease respond to a discontinuous administration (usually 3 subcutaneous injections per day), and the IGF1 level is normalized in 50 percent of the cases. No long-term desensitization and no rebound phenomenon after drug withdrawal have been observed. Clinical improvement is obvious, even in cases with partial response to treatment. The dose required to obtain maximum response may vary from one patient to another, and resistance to the peptide has been observed in a few patients. This resistance does not seem to be related solely to the absence of somatostatin receptors on the tumours. The principal side-effect of octreotide treatment is the occurrence of gallstones. In some patients, continuous subcutaneous injection gives a better result with a lower dose. Other ways of administration (nasal or oral) have been tested or are being evaluated.
 ...
PMID:[Octreotide, analog of somatostatin. Pharmacological properties and therapeutic applications in pituitary endocrine tumors]. 790 19

Dilated cardiomyopathy associated with acromegaly is rare, but may improve with octreotide, a somatostatin analogue. The authors give the first description here of paradoxical worsening in cardiac function during such treatment, with the onset of episodes of acute decompensation following each attempt at starting treatment. Thus worsening was confirmed objectively by a challenge test with octreotide: increased dyspnea, fall in shortening fraction and in echocardiographic cardiac output (of 17 to 14% and 4 to 3 l/min respectively), a decrease in isotopic ejection fraction from 15 to 6% and this in parallel with efficacy regarding hormone levels of GH and IGF1 and a reduction in tumour size by CT scan. No further episode of decompensation occurred after treatment was stopped permanently. The patient underwent a transplant 3 months later. Suppression of the positive inotropic effect of GH by octreotide, associated with an increase in peripheral resistance is suggested. A negative inotropic effect of this hormonal analogue on too advanced a case of heart disease is also a possibility.
 ...
PMID:[Dilated cardiomyopathy in acromegaly worsening under octreotide treatment. Apropos of a case]. 849 2

Anorexia nervosa (AN) is a chronic disease in which an enhanced GH response to GHRH, a paradoxic increase after TRH and LHRH, and low IGF1 levels may be present according to the patient's clinical state. It is well known that the GH hypersecretory state commonly found in the "acute phase" of AN is restored with weight gain. The new synthetic hexapeptide, Hexarelin (HEX), which is chemically similar to GH-releasing peptide 6, has recently been shown to possess a stronger GH-releasing activity than GHRH in humans and to share a synergistic effect with GHRH when administered intravenously. Indeed, HEX shows a slight cortisol and PRL-releasing activity. The aim of the study was to evaluate the effect of i.v. administration of old (GHRH) and new (HEX) GH-releasing peptides on GH, PRL and cortisol secretion in 9 AN patients in the "recovery phase" of the disease, after partial but significant weight gain. For controls we studied 7 normal cycling women. No significant difference in GH secretion after GHRH was found between AN and controls. GHRH was not able to release cortisol or PRL either in AN or controls. HEX produced a significantly (p < 0.05) higher GH peak in controls than in AN, while GH AUC was slightly but not significantly higher. Indeed, only in controls, HEX was a stronger GH-releasing peptide than GHRH. These findings could be explained by the fact that, in AN, GH secretion is already stimulated both by reduced IGF1 levels and by increased GHRH/somatostatin ratio. As reported in the literature, the action of HEX action is only slightly influenced by variations in somatostatin tone. It therefore appears likely that the absolute or relative GHRH increase present in AN could partially mimic the unknown hypothalamic factor necessary for HEX action on the hypophisis and that, following a structural modification of pituitary HEX receptors, GHRH would become able to bind to HEX receptors on somatotropic cells. Consequently, the pituitary cells would already be over-activated and so unable to respond maximally to HEX stimulation. Indeed, in AN, GHRH might play a role of negative modulation in the control of HEX action. Finally, in our study HEX was able to produce a persistent PRL release in controls but not in AN, thus suggesting that its action could be partially dependent on the estrogen milieu, while it stimulated cortisol secretion only transiently in the patients studied.
 ...
PMID:Hexarelin is a stronger GH-releasing peptide than GHRH in normal cycling women but not in anorexia nervosa. 925 4

The use of somatostatin analogues for the treatment of acromegaly is now well established. Recently long-acting preparations of octreotide and lanreotide have been introduced. In this study we have assessed the efficacy and tolerability of the long acting somatostatin analogue octreotide LAR in patients with acromegaly, and compared it with lanreotide SR. Five patients with active acromegaly were recruited; they were treated with lanreotide SR for 6 months and then, following a wash-out period, received octreotide LAR for 6 months. They were assessed at baseline, 3- and 6-months, by clinical score, GH and IGF1. Adverse effects were carefully monitored. Both treatments effectively reduced GH and IGF1 levels. Four of five patients achieved a mean GH level of < 2.5 ng/ml with both drugs; with octreotide LAR only, these patients also had GH < 1 ng/ml after oral glucose loading. The clinical symptoms score improved significantly with octreotide LAR, as did the ring size; the clinical score correlated significantly with GH. Blood glucose was not adversely affected. All patients experienced minor GI symptoms with lanreotide SR, but less frequently with octreotide LAR. Both drugs caused biliary stasis and had a tendency to form biliary sludge. Octreotide LAR proved effective for the treatment of acromegaly and was well tolerated. Octreotide LAR had some advantages over lanreotide SR, although the differences were not great.
 ...
PMID:Long-acting octreotide LAR compared with lanreotide SR in the treatment of acromegaly. 1114 97

We describe the first case of a 36 year-old male patient with a somatotropin and thyreotropin secreting pituitary adenoma, co-treated by a long-acting releasing somatostatin analog (Octreotide) and a GH receptor antagonist (Pegvisomant). The patient normalized his biological disease activity reflected by hormone levels but his tumor size remained unchanged as measured by MRI. The co-treatment was well tolerated and induced a synergic effect on IGF1 levels that allowed us to use low doses of both therapies.
 ...
PMID:An unusual somatotropin and thyreotropin secreting pituitary adenoma efficiently controlled by Octreotide and Pegvisomant. 1684 Sep 17

The usefulness of the acute octreotide test in the selection of acromegalic patients for chronic somatostatin depot analogues treatment is controversial. The aim of the present study was to determine its accuracy for chronic response prediction, and the reliability of a short version of the classic 6-hour test. The data from 26 acromegalics (19 women, 7 men, mean age 52.6+/-13.1 years) studied with an acute octreotide test (6 hours sampling for GH measurement after octreotide 100 microg s. c.) were retrospectively analyzed. Eighteen of them followed chronic somatostatin depot analogues treatment for 12 months. GH nadir was always detected at 2 hours (mean decrease 75.9+/-24%). GH levels at 2 hours positively correlated with the other time-points (r(s) 0.97, 0.98, 0.97, 0.96 at 3, 4, 5 and 6 h, respectively; p<0.0001). During chronic treatment with maximal effective dose for 12 months, 61% of the patients achieved IGF1 <3 SD and 22% reached IGF1 <2 SD. GH nadir correlated with IGF1 decrease at 12 months (r(s) 0.76, p<0001). GH nadir of 9.2 ng/ml predicts IGF1 <3 SD with 82% sensitivity and 58% specificity (75% PPV, 67% NPV); for IGF1<2 SD, 75% sensitivity and 58% specificity are obtained for GH nadir 3.6 ng/ml, with 33% PPV and 89% NPV. Acute octreotide test reliably predicts response to long-term treatment; the short, 2-hour version is fully informative for therapeutic decisions in acromegalic patients.
 ...
PMID:A short acute octreotide test for response prediction of long-term treatment with somatostatin analogues in acromegalic patients. 1839 73


1 2 3 4 Next >>