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

Growth hormone (GH) secretion in the elderly is generally diminished although there are marked individual differences ranging from normal GH secretion and normal levels of insulin-like growth factor (IGF)-I through low GH and subnormal IGF-I. It is assumed that the reduced central cholinergic activity leading to unrestrained somatostatin release leads to impaired GH secretion. The somatopause, if it occurs at all, is, in contrast to the menopause, a subtly developing physiological event. The menopause often causes severe symptoms that justify hormone replacement therapy, but the somatopause is a physiological event at the end of the lifespan with no acute symptoms that can be attributed to GH deficiency with certainty. Whether the non-specific symptoms of old age, i.e. truncal obesity, muscle atrophy, decreasing energy, and mental disorders, can be--even partially--blamed on decreased GH secretion is unclear. Thus, GH therapy in elderly patients, in the absence of pituitary disease cannot be recommended. In addition, the following has to be considered: 1) GH has to be given by subcutaneous injection, which may be technically difficult in elderly patients. 2) It is difficult to find the right individual dosage of GH since elderly patients may show increased sensitivity to GH therapy (compared with children) or may be GH-resistant. 3) Manifestation of diabetes mellitus may be enhanced in elderly patients. 4) The elevation of IGF-I levels may enhance the progression of malignant disease; it has been shown that the concentration of IGF-I in the circulation correlates to the frequency of prostatic cancer. Furthermore, acromegalic patients have a higher frequency of colonic polyps and gastrointestinal malignancies. 5) Even if problems such as dosage, mode of application and the questions of safety are resolved, the present costs of GH therapy will not allow to advocate GH treatment of all elderly patients with low levels of IGF-I. However, since some patients seem to benefit from GH therapy in senescence, further studies are needed. There may be a subset of elderly patients in whom GH treatment is useful. However, unless these patients are included in a study protocol, GH treatment should not be given to elderly patients in the absence of pituitary disease.
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PMID:The somatopause is no indication for growth hormone therapy. 1044 83

Octreotide is a long-acting somatostatin analog that has been shown to have various effects in diabetes. This study was performed to evaluate whether octreotide affects the vascular complications of diabetes mellitus. Albuminuria and serum thrombomodulin were used as markers of vascular and renal dysfunction. We studied the effect of octreotide in 27 patients with insulin-dependent diabetes mellitus (IDDM). They received 200 microg octreotide per day over a period of 6 months. As a marker of endothelial cell damage, we measured the serum thrombomodulin level. We also measured urinary albumin excretion, hemoglobin A1c (HbA1c), insulin-like growth factor-1 (IGF-1), and other parameters. IGF-1 decreased from 123 ng/mL before treatment to 114 ng/mL after 6 months of octreotide treatment (P = .009), while no significant change was observed in the unblinded control group (from 103 ng/mL to 102 ng/mL after 6 months of treatment). Urinary albumin excretion in patients with macroalbuminuria declined from 1,124 mg/L before octreotide treatment to 556 mg/L after 6 months of treatment (P < .05), whereas no change was observed in the control group. There was also a reduction of the plasma thrombomodulin level from 61.8 ng/mL to 46.1 ng/mL (P < .07) after 6 months of treatment. Furthermore, HbA1c decreased from 8.75% +/- 1.27% to 8.12% +/- 1.23% (P < .07) after octreotide treatment.
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PMID:Octreotide (somatostatin analog) treatment reduces endothelial cell dysfunction in patients with diabetes mellitus. 1053 84

Somatostatin is a cyclic tetradecapeptide hormone. It was initially isolated from bovine hypothalami. Somatostatin inhibits endocrine and exocrine secretion, as well as tumor cell growth, by binding to specific cell-surface receptors. Its potent inhibitory activity is limited, however, by its rapid enzymatic degradation and the consequently short plasma half-life. Octreotide is a short somatostatin analogue with increased duration of action compared with somatostatin. Preclinical studies have focused on the anticancer effects of octreotide and the related somatostatin analogues. In vitro, at nanomolar concentrations, these analogues inhibit the growth of tumor cells that express high-affinity somatostatin receptors. Accordingly, such analogues potently inhibit the growth of somatostatin receptor-positive tumors in various rodent models. The range of cancers susceptible to octreotide and related somatostatin analogues includes mammary, pancreatic, gastric, colorectal, prostate, thyroid, and lung carcinomas. Moreover, an indirect antiproliferative effect of somatostatin analogues is achievable in somatostatin receptor-negative tumors whose growth is driven by factors (e.g., gastrin, insulin-like growth factor-1) that become down-regulated by somatostatin. The clinical effect of somatostatin analogues in terms of tumor response in cancer patients is a subject of controversy, however. Most responses have been seen in patients with pancreatic cancers.
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PMID:The significance of somatostatin analogues in the antiproliferative treatment of carcinomas. 1062 87

Galanin (GAL) elicits growth hormone (GH) release in normal subjects through interaction with hypothalamic somatostatin. GAL also stimulates GH-releasing hormone (GHRH) secretion in vitro. In rats, GAL is able to stimulate prolactin (PRL) release, but this effect is not clear in humans. We have thus investigated GAL effects on GH and PRL release in patients with anorexia nervosa (AN), known to have altered regulation of the GH-insulin-like growth factor axis and PRL dynamics, and compared the effects of GHRH and GAL on GH and PRL secretion in AN and normal healthy subjects. Eight women with AN (15 to 27 years; body mass index [BMI], 17 to 19.5 kg/m2) were treated with (1) GHRH 50 microg intravenous (IV) injection, (2) porcine GAL 500 microg infusion from -10 to +30 minutes, and (3) 135-minutes saline infusion as a control, respectively. Both peptides induced a significant increase in plasma GH in AN patients (peak level, 27.41 +/- 5.50 microg/L after GAL and 18.97 +/- 2.67 microg/L after GHRH). When data for AN patients and the control group were compared, GH peak levels after GAL were significantly higher in AN patients (27.41 +/- 5.50 v 13.64 +/- 2.32 microg/L), while GH peak levels after GHRH were not different between the 2 groups (18.97 +/- 2.67 v 15.98 +/- 3.88 microg/L). PRL levels significantly increased after both GHRH (peak, 11.70 +/- 2.80 microg/L) and GAL (peak, 18.02 +/- 5.10 microg/L) treatment in AN patients, but not in normal subjects. We conclude that GAL stimulates exaggerated GH release in AN patients as compared with normal controls, suggesting a dual hypothalamic interaction via both an increase in endogenous GHRH and a decrease in somatostatin secretion. Finally, GAL may act as a PRL secretagogue in AN patients.
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PMID:Effects of galanin on growth hormone and prolactin secretion in anorexia nervosa. 1069 Sep 37

Endotoxin (LPS), a membrane component of gram-negative bacteria produces multiple endocrine and metabolic effects that mimic those seen in acute sepsis. It induces species-dependent alterations of the growth hormone (GH) axis that may participate in the shift of the metabolism towards catabolic events. Humans and sheep show increased GH secretion in response to LPS, as opposed to rats, which have been the most studied. The purpose of our work was to evaluate the effects in intact rams of an acute intravenous administration of a high dose of LPS on the insulin-like growth factor (IGF)-I/IGF-binding proteins (IGFBPs) system and to analyse the temporal relationship of GH axis changes with those of several hormonal and metabolic parameters such as somatostatin, cortisol, insulin, and glucose. LPS induced a late moderate decrease of total IGF-I plasma levels following a 5-h steady-state period (-26.6+/-4. 2%, P<0.05, 9 h after LPS), despite a biphasic and sustained increase of GH secretion in the same animals (2.48+/-0.39 ng/ml 2 h after LPS and 2.7+/-0.37 ng/ml 5 h after LPS vs 0.77+/-0.10 before LPS; Briard et al. 1998a). Western ligand blot analysis in IGFBPs showed an early short-lasting increase in IGFBP-1 (188.8+/-39% P<0. 05, 3 h after LPS). No significant change was seen for either IGFBP-2, -3 or -4. We observed a marked and sustained increase in cortisol (128.18+/-7.21 ng/ml 3 h after LPS, vs 21.17+/-4.22 before LPS). Insulin also increased (27.69+/-3.90 microU/ml 3 h after LPS, vs 13.48+/-1.69 before LPS) and its burst coincided with that of IGFBP-1. Moderately decreased IGF-I and increased IGFBP-1 plasma levels contrasted with the sustained increase in GH secretion that we recently described, thereby suggesting that endotoxin causes a state of resistance to GH. This may be exacerbated by reduced IGF-I bioavailability and/or action, and which may participate in the pathophysiology of the catabolic state seen in sepsis. The temporal analysis of hormone responses suggests that endotoxin-induced alterations of the IGF-I/IGFBPs system may involve the prolonged and substantial somatostatin rise that we recently demonstrated, together with an increase in glucocorticoid and cytokine as more generally assumed.
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PMID:IGF-I/IGFBPs system response to endotoxin challenge in sheep. 1069 76

Insulin-like growth factor II (IGF-II) appears to play an important role during fetal life in cell growth and differentiation in several organs, including the pancreas. In the present study we investigated the cellular localization of IGF-II in human fetal pancreas at 16, 18 and 22 embryonic weeks and compared it with adult pancreas. Single and double immunofluorescence methods were used to study co-localization of IGF-II with the four major islet hormones - insulin, glucagon, somatostatin, pancreatic polypeptide - and with islet amyloid polypeptide (IAPP). Distinct IGF-II immunoreactive (IR) cells were found in the endocrine, but not in the exocrine, pancreas. The intensity of IGF-II immunoreactivity was more pronounced in the fetal than in the adult pancreas. In fetal pancreas IGF-II immunoreactivity was observed in virtually all insulin-IR cells and in subsets of the glucagon, somatostatin and IAPP cells. In the adult pancreas, IGF-II immunoreactivity was found in insulin/IAPP cells only. Our results suggest a broader effect of IGF-II in fetal endocrine pancreatic cells than in the adult.
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PMID:Insulin-like growth factor II in human fetal pancreas and its co-localization with the major islet hormones: comparison with adult pancreas. 1081 Feb 88

Recent clinical studies have demonstrated an increase of urinary albumin excretion (UAE) at rest in acromegalic patients and, on the other hand, a reduced UAE in patients with growth hormone (GH) deficiency. Physical exercise is known to induce abnormal UAE in patients with diabetes, probably unmasking early glomerular alterations. The effect of exercise on UAE in acromegaly is not known. Moreover, the effect of acute but sustained GH inhibition in acromegaly on UAE at rest and after exercise has never been studied. The aim of our study was to evaluate the acute short-term effects of slow-release lanreotide (SR-L), a long-acting somatostatin analog, on UAE and alpha1-microglobulinuria (A-1-M), a marker of renal tubular damage, at rest and after exercise in 7 normotensive patients with active acromegaly and normal renal function (4 males and 3 females; mean age, 53 +/- 3.1 years; body mass index [BMI], 27.3 +/- 1.1 kg/m2) at baseline and 7 and 14 days after SR-L injection (30 mg). Two of the acromegalic patients were microalbuminuric at rest, and in other 3 cases, UAE was in the borderline range (10 to 20 microg/min). At baseline in the acromegalic subjects, we found a significant increase in UAE at rest with respect to 7 normal subjects considered as a control group. GH and insulin-like growth factor-1 (IGF-1) were also reduced compared with baseline 7 and 14 days after SR-L injection (GH, 13.4 +/- 7.3 and 13.61 +/- 7 v 18.5 +/- 9.3 microg/L, P < .05; IGF-1, 230 +/- 53 and 255 +/- 54 v 275 +/- 64 microg/L). Concomitantly, we observed a significant decrease of UAE at rest and after exercise and 7 and 14 days after SR-L injection as compared with baseline values (27.3 +/- 20.5 and 18.2 +/- 13.7 v 35.3 +/- 12.8 microg/min, P < .05; exercise, 48.5 +/- 24.1 and 18.6 +/- 6.8 v68.3 +/- 39.7 microg/min, P < .05). A-1-M always remained in the normal range (< 12 mg/L) both at rest and after exercise. We can thus conclude that in acromegaly, submaximal exercise induces abnormal increases in microalbuminuria. We hypothesize that this phenomenon may be due to the functional glomeruler involvement. SR-L can significantly reduce UAE at rest and after exercise in the short-term in acromegaly, probably via a decrease in circulating GH levels.
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PMID:Exercise-induced microalbuminuria in patients with active acromegaly: acute effects of slow-release lanreotide, a long-acting somatostatin analog. 1083 Nov 75

Transsphenoidal surgical resection is the primary therapy for acromegaly caused by GH secreting pituitary adenomas. Medical therapy for patients not controlled by surgery includes primarily somatostatin analogs and secondarily dopamine agonists, both of which inhibit pituitary growth hormone secretion. A novel GH receptor antagonist (pegvisomant) binds to hepatic GH receptors and inhibits peripheral insulin-like growth factor-1 generation. Six patients resistant to maximal doses of octreotide therapy received pegvisomant - three received placebo or pegvisomant 30 mg or 80 mg weekly for 6 weeks and three received placebo and pegvisomant 10-20 mg/d for 12 weeks. Thereafter, all patients received daily pegvisomant injections of doses determined by titrating IGF-1 levels. Serum total IGF-1 levels were normalized in all six acromegalic patients previously shown to be resistant to somatostatin analogs via a novel mechanism of peripheral GH receptor antagonism. The GH receptor antagonist is a useful treatment for patients harboring GH-secreting tumors who are resistant to octreotide.
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PMID:Growth hormone receptor antagonist therapy in acromegalic patients resistant to somatostatin analogs. 1094 11

Recently, the medical approach to patients with secreting and clinically non-functioning pituitary adenomas has received great impulse thanks to the availability of new, selective and long-lasting compounds with dopaminergic activity, such as cabergoline, and of somatostatin analogues provided in slow-release formulations, such as lanreotide and octreotide long acting release (LAR). In particular, the use of cabergoline has induced control of hyperprolactinaemia and tumour shrinkage in the great majority of patients with micro- and macroprolactinomas. Cabergoline treatment restores fertility both in women and men, and partially improves osteoporosis, one of the major complications of hyperprolactinaemia. In acromegaly, disease control (growth hormone [GH] <2.5-1.0 microg/l as a fasting or glucose-suppressed value, respectively, together with age-normalised insulin-like growth factor [IGF]-I) is achievable in more than half of patients receiving treatment with lanreotide or octreotide-LAR. Improvement in cardiomyopathy, sleep apnoea and arthropathy has been reported during GH/IGF-I suppression after pharmacotherapy. A synthetic GH analogue, B2036-PEG, that antagonises endogenous GH binding to its receptor-binding sites and a GH-releasing hormone antagonist that blocks the effect of this releasing factor on the hypothalamus and pituitary are presently under investigation in acromegaly. Preliminary studies have clearly demonstrated the effectiveness of the GH receptor antagonist in suppressing IGF-I levels in acromegalic patients previously unresponsive to somatostatin analogues. Beneficial effects of subcutaneous octreotide and lanreotide have also been reported in adenomas secreting thyroid-stimulating hormone, while the results of treatment with dopamine agonists or somatostatin analogues remain disappointing in patients with clinically non-functioning adenomas. In these patients the possibility of visualising in vivo the expression of D(2) receptors using specific radiotracers such as (123)I-methoxybenzamide has allowed selection of patients likely to respond to cabergoline. Scant effects of pharmacotherapy have also been reported in patients with adenomas secreting adrenocorticotropic hormone. However, some preliminary data suggest a potential use of cabergoline in combination with ketoconazole, or alone, in selected cases of Cushing's disease or Nelson's syndrome.
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PMID:New medical approaches in pituitary adenomas. 1097 Nov 10

Cardiovascular disease is the most severe complication of acromegaly accounting for the increased mortality of these patients. Recently, the slow-release form of octreotide (OCT; Sandostatin LAR, OCT-LAR), for im injection every 28 days, was reported to induce suppression of GH levels below 7.5 mU/L (2.5 microg/L) in 39-75% of patients, and normalization of insulin-like growth factor (IGF)-I levels for age in 64-88% of patients, with an excellent patients' compliance. The aim of the present study was to investigate the early effect of OCT-LAR treatment on the left ventricular (LV) structure and performance in 15 somatostatin analog-naive patients with acromegaly (GH, 94.8 +/- 24.9 mU/L; IGF-I, 757.9 +/- 66.6 microg/L), focusing on the early effect of GH and IGF-I suppression on the heart. Cardiac structure was investigated by echocardiography, whereas LV performance was investigated by gated-blood-pool scintigraphy, before and after 3 and 6 months of treatment with OCT-LAR. OCT-LAR was initially administered im, at a dose of 20 mg every 28 days, for 3 months. In six patients, the dose was then increased to 30 mg every 28 days to achieve disease control, which was considered when fasting and/or glucose-suppressed GH values were below 7.5 and 3.0 mU/L, respectively, together with IGF-I values within the normal range for age. The treatment with OCT-LAR for 6 months induced a significant decrease of GH (to 12.9 +/- 3.0 mU/L) and IGF-I levels (to 340.3 +/- 40.2 microg/L) in all 15 patients. After 6 months of treatment, the percent IGF-I suppression was 52.8 +/- 4.4%, and serum GH/IGF-I levels were normalized in 9 patients. A significant decrease of LV mass index (LVMi), interventricular septum thickness, and LV posterior wall thickness was observed in all 15 patients after 3 and 6 months of OCT-LAR treatment: LVMi was decreased by 19.1 +/- 2.0% without any difference in patients with (19.9 +/- 2.7%) or without disease control (17.8 +/- 3.3%). Among the 11 patients with LV hypertrophy, 6 normalized their LVMi after treatment. At study entry, an inadequate LV ejection fraction (LVEF) at rest (<50%) was found in 5 patients (33.3%), whereas an impaired response of LVEF at peak exercise (<5% increase of basal value) was found in 9 patients (60%). A significant increase in LVEF, both at rest (from 51.6 +/- 2.6 to 58.1 +/- 1.7%, P < 0.01) and at peak exercise (from 51.6 +/- 2.3 to 60.2 +/- 2.4%, P < 0.001) was found in patients with (as compared with those without) disease control (from 55.2 +/- 3.8 to 58.0 +/- 4% and from 61.8 +/- 4.6 to 61.8 +/- 3.4%, respectively). Among the 5 patients with inadequate LVEF at rest, all but 1 regained a normal LVEF after 6 months of treatment; whereas, among the 9 patients with an impaired response of the LVEF at peak exercise, 3 patients normalized, 4 improved, and 2 impaired their responses after treatment. The percent of IGF-I suppression was significantly correlated with the percent increase of resting LVEF (r = 0.644, P < 0.01). Exercise duration (from 6.0 +/- 0.7 to 7.3 +/- 0.7 min) and capacity (from 69.0 +/- 8.2 to 80 +/- 7.8 watts) were increased in the 15 patients considered as a whole, but the improvement in the exercise response was significant only in patients with disease control (P < 0.01 and P < 0.05, respectively) who also had an increase in the peak ejection rate (P = 0.03). No change in hemodynamic parameters, either at rest or at peak exercise, was found after treatment with OCT-LAR in the 15 patients. In conclusion, the results of the present study demonstrate that OCT-LAR im injections every 28 days induces a sustained suppression of GH levels and IGF-I levels in all acromegalic patients, allowing achievement of disease control in 60% of patients after 6 months of treatment. The sustained suppression of IGF-I levels was followed by a significant reduction of LVMi in all patients already after 3 months of treatment, with recovery of LV hypertrophy in 6 of 11 patients. (ABSTRACT TRUN
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PMID:Cardiovascular effects of depot long-acting somatostatin analog Sandostatin LAR in acromegaly. 1099 98


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