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)

This review evaluates the efficacy, tolerability, and safety of continuous subcutaneous infusion (CSI) relative to intermittent subcutaneous injection (ISI) of the somatostatin analog, octreotide in the treatment of acromegaly. Data was extracted from five clinical series using CSI octreotide in acromegaly, six reports comparing CSI to ISI, and three studies comparing pulsatile subcutaneous infusion (PSI) to ISI. Effects of each drug regimen on the control of growth hormone (GH), insulin-like growth factor (IGF-1), clinical symptomatology, pituitary tumor size, and adverse effects were evaluated. Normalization of serum GH or IGF-1 levels, as well as improvement in clinical symptoms was reported in the majority of the patients studied. Cases in which pituitary adenomas decreased in size were also documented during the study period. When the effects of CSI were compared with ISI, a more pronounced control of GH and IGF-1 was observed. In addition, diurnal GH fluctuation during CSI was significantly reduced relative to ISI in two reports. Moreover, in two patients, CSI achieved similar clinical and biochemical effects at lower doses than when the drug was given by ISI. Finally, adverse effects with CSI may be less severe than with ISI. Continuous subcutaneous infusion of octreotide produced biochemical improvement in 67 of the 88 patients reviewed. When compared with ISI, CSI induced more pronounced biochemical control, often with less fluctuation in GH and IGF-1 levels. Because of a lack of data, definite conclusions regarding the differences between regimens on clinical symptomatology and tolerability could not be discerned. A large prospective, long-term randomized crossover study is recommended to make these determinations.
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PMID:Continuous versus intermittent subcutaneous infusion of octreotide in the treatment of acromegaly. 775 14

Streptozotocin diabetes prevents induction of pancreatic tumors in several animal models, suggesting a pivotal role for islet cell products in the pathogenesis of pancreatic cancer. To test the hypothesis that altered gastrointestinal peptide levels in streptozotocin diabetes influence tumor growth, human pancreatic cancer cells (MIA PaCa-2) were implanted subcutaneously into streptozotocin diabetic nude mice. After 3 weeks, tumors in the control group weighed 43 mg and tumors in the diabetic group weighed 12 mg (P < 0.001). Plasma insulin and IGF-1 levels were significantly decreased in the streptozotocin-treated animals compared to those of control (insulin: 23 microU/ml vs 31 microU/ml, P < 0.001; IGF-1: 254 ng/ml vs 324 ng/ml, P < 0.001). In contrast, somatostatin and glucagon were significantly elevated in the streptozotocin diabetic group relative to control levels (somatostatin: 179 pg/ml vs 54 pg/ml, P < 0.001; glucagon: 290 pg/ml vs 134 pg/ml, P < 0.001). Competitive binding studies revealed specific cell surface receptors for insulin (Kd = 15.5 nM), IGF-1 (Kd = 30.0 nM), and somatostatin (Kd = 2.5 nM) on the MIA PaCa-2 cells. Receptors for glucagon were absent. In an in vitro cell proliferation assay, cell division was promoted by insulin (P < 0.01, max + 11%) and IGF-1 (P < 0.01, max + 10%). Somatostatin inhibited cell division (P < 0.01, max - 18%). No effect was seen with glucagon. The growth of pancreatic cancer, particularly in diabetes, may be influenced by gut peptides in a receptor-dependent fashion.
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PMID:GI hormonal changes in diabetes influence pancreatic cancer growth. 779 56

Recently somatostatin (SST) intra-articular administration has been used in the treatment of some rheumatoid diseases such as rheumatoid arthritis, psoriatic arthritis and osteoarthritis with encouraging results. The aim of this study was to evaluate the efficacy and tolerability of SST intra-articularly injected, involving 20 patients with knee osteoarthritis. Treatment consisted of 4 injections, administered weekly, each of 750 mcg SST. Additionally, in six of them we evaluated the circulating levels of the insulin-like growth factor (IGF)-1 at the base-line time and then every 7 days (immediately before each dose of SST). The results revealed an improvement in pain and in joint function after intra-articular SST, confirmed by statistical analysis. The circulating levels of IGF-1 did not show significant variations following intra-articular administration of SST. The excellent tolerability and the absence of unwanted side-effects with SST allow us to foresee that intra-articular SST could be used in cases of painful knee osteoarthritis, especially in those patients in which other drugs are not appropriate. Moreover, in the absence of modifications of serum levels of IGF-1, SST could be used in athletes.
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PMID:Intra-articular injection of somatostatin in knee osteoarthritis: clinical results and IGF-1 serum levels. 783 29

Treatment of Acromegaly has been improved by the development of the somatostatin analogs characterized by an increased specificity and longer duration of action. One of these analogs-Lanreotide- (Somatuline) is supplied under a slow release formulation and does not require several daily injections like other analogs presently available. The clinical pharmacodynamic studies that have been conducted in healthy and acromegalic patients show that the i.m. injection of a single dose of this slow-release formulation leads to a significant decrease of the plasma GH and IGF-1 levels. This effect lasts at least 14 days. The Lanreotide slow-release formulation has been used to treat 123 acromegalic patients who presented with a still evolutive disease after conventional therapy. The product was given at a 30 mg-dose every 10 or 14 days during a 3-to 24-month period. This treatment led to a reduction of the symptoms and to a decrease of GH hypersecretion. GH and IGF-1 levels have been normalized respectively in 46% and 32% of the patients. The observed results allow to conclude to an immediate efficacy of the treatment (without escape sign). The adverse drug events are minor and transitory. The antitumor effects are modest and inconstant. The slow release formulation seems to provide the patients with a better quality of life, as compared to the several daily injections.
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PMID:[Treatment of acromegaly with a new slow release somatostatin analog, lanreotide]. 786 83

This study was undertaken to examine the effects of increasing doses of rat somatocrinin (GRF) with or without a somatostatin antiserum (SS-ab) on serum hormone and metabolic concentrations, as well as serum and duodenal cholecystokinin (CCK) and antral gastrin concentrations. 24-day-old male Sprague-Dawley rats were injected twice daily s.c. (10:00 and 16:30) for 14 consecutive days with either saline or rat GRF (1-43) NH2 (4 and 20 micrograms/kg) in gelatin. Three other groups of animals received the same treatment in association with the SS-ab given i.p. every other day making up the 6 groups of 12 animals in a 2 x 3 factorial design experiment. GRF treatment increased circulating growth hormone (GH) concentrations in a dose-dependent manner, alone or in combination with the SS-ab; the SS-ab treatment alone or combined with GRF also increased GH concentrations. Total hypophyseal GH content was increased (P < 0.05) by the GRF treatment alone. Serum levels of IGF-1, acetoacetate, alpha 2 globulin and antral gastrin were all increased by the GRF treatment with plateaus observed for antral gastrin and serum IGF-1 levels at the intermediary dose of GRF. Serum concentrations of T4 were reduced at the 4 micrograms/kg dose of GRF. Serum concentrations of CCK were increased by the SS-ab treatment alone, an effect reversed by increasing doses of GRF. Rat GRF produced a dose-dependent increase and decrease of alpha 2 globulin and albumin, respectively. These data indicate that GRF, probably via its effect on GH release, influences gastrointestinal hormone levels which are implicated in gastrointestinal organ growth and digestive processes.
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PMID:Effects of GRF with or without a SRIF antiserum on GH, IGF-1, thyroxin, cholecystokinin, gastrin and metabolite concentrations in growing rats. 795 Sep 3

Glucocorticoids (GCs) modulate the somatotropic axis at a genomic and a non-genomic level. Critical concentrations of steroids not only determine somatotrope differentiation but also enhance growth hormone (GH) gene expression. At a cellular level GH-releasing hormone (GHRH) and somatostatin (SS) are the two principal neuropeptides involved in the release of GH. In vitro data indicates that steroids enhance GH release by altering the affinity and the density of GHRH receptors. In addition, they reduce the sensitivity of the somatotrope to SS and decrease IGF-1 induced negative feedback on GH secretion. The net effect is an enhancement of GH release.
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PMID:Growth hormone secretion: the role of glucocorticoids. 809 52

It was previously demonstrated that initial kidney hypertrophy has been seen in diabetic animals and somatostatin infusion suppresses GFR and serum insulin like growth factor (IGF-1) in diabetic patients. I studied the effects of somatostatin analogue (octreotide) on glomerular hypertrophy in diabetic rats. The animals were randomized into six groups: two groups of streptozocin (STZ) induced diabetic, insulin-treated diabetic and non-diabetic rat groups. One of these three groups were treated with two daily subcutaneous injections of octreotide (10 micrograms x 2) for a period of five weeks. In diabetic rats, body weight, blood sugar, glucose excretion, serum insulin, urinary volume, urinary protein, serum creatinine or creatinine clearance did not differ in diabetic rats with vs. without octreotide injection, but kidney weight (2.97 +/- 0.12 vs. 3.28 +/- 0.08 mg, P < 0.05; mean +/- SEM) and estimated glomerular volume (9.13 +/- 0.22 vs. 12.77 +/- 0.34 x 10(5) microns 3, P < 0.001) were all reduced in diabetic rats with octreotide when compared with untreated diabetic rats. In non-diabetic rats, octreotide reduced body weight (340.3 +/- 6.5 vs. 367.1 +/- 3.8g, P < 0.01) and kidney weight (2.29 +/- 0.08 vs. 2.51 +/- 0.04 g, P < 0.05) when compared with non-diabetic rats without octreotide. Urinary protein excretion (8.57 +/- 1.39 vs. 14.29 +/- 1.53 mg/day, P < 0.05), serum 1GF-1 concentration (956.3 +/- 180.7 vs. 1546.1 +/- 88.1 mg/day, P < 0.05) and estimated glomerular volume (7.69 +/- 0.16 vs. 9.72 +/- 0.15 x 10(5) microns 3, P < 0.001) significantly differed in insulin treated diabetic rats with vs. without octreotide.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Octreotide suppresses the kidney weight and glomerular hypertrophy in diabetic rats]. 850 54

The manipulation of the inflammatory and hormonal responses may produce, on one hand, positive effects, and, on the other hand, potentially negative effects. The modification of the neuro-endocrine-humoral pattern may become more important and effective than the supply of nutrients. In this article we bring an up date of the role of insulin, anabolic steroids, blocking the catabolic hormones, phenobarbital, somatostatin, clenbuterol and metaprorenol, growth factors: GH and IGF-1, cytokines, and anti-cytokines sera. The use of GH, IGF-1, and of the epidermal and or colonic growth factors, along with a blocking of the cytokines, the manipulation of the lipidic mediators, and the supply of classical nutrients, specific to the aggression situation, may improve the protein synthesis and tissue repair. It may at the same time both decrease the loss of body proteins as well as promoting and acceleration of the recovery, shortening the hospital stay and reducing the convalescence time. The future seems to point towards molecular and cellular biotechnology and towards "nutritional" pharmacology, which contemplates the effects of growth factors, the recent advances in the field of cytokine modulation, and the manipulation of the binomer nutrient-medication.
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PMID:[Hormones, growth factors, and drugs in metabolism and nutrition]. 851 56

The physiological role of GH secretion on growth retardation remains to be elucidated especially in patients with beta-thalassemia. In the present study, we investigated IGF-1 circulating levels as well as GH release following GHRH alone or combined with some inhibitors of somatostatin: pyridostigmine and arginine. In thalassemic patients lower IGF-1 circulating levels appear to be negatively correlated with both aspartate aminotransferase and alanine aminotransferase as well as with ferritin circulating levels indicating a probable role of hepatic hemosiderosis in IGF-1 production. The authors however suggest that reduced IGF-1 secretion is not the main cause of growth retardation since this would have elicited an enhanced response of GHRH in the presence of a normal hypothalamic pituitary axis. In contrast, they noticed that GH response to GHRH when expressed as area under the curve was lower in thalassemic patients compared to controls. The combination of GHRH with either pyridostigmine or arginine induced a GH secretion in thalassemics which was comparable to that of controls. The results of this study lead to conclude that the alteration of GH secretion is due, in such patients, to an increased somatostatin activity.
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PMID:GH secretion in thalassemia patients with short stature. 852 76

Hormone replacement should provide a serum hormone profile similar to that found in normal physiology. This is generally impractical because hormones are usually released episodically and therefore require frequent administration. However, rather than replacing the hormone directly, in theory, one could administer a mimic or amplifier of the pulse generator that controls pulsatile release of the particular hormone. Using growth hormone (GH) as a paradigm we sought such a mimetic that would provide episodic GH release when administered by the oral route. A GH secretagogue MK0677, is described that has these ideal properties; following oral administration MK0677 amplifies episodic GH release. Mechanistically, it synergizes with growth hormone releasing hormone (GHRH) through a receptor and signal transduction pathway distinct from that of GHRH and is a functional antagonist of somatostatin (SRIF). MK0677 also acts on the arcuate nucleus and appears to stimulate GHRH release. By using 35S-MK0677, a new G-protein coupled receptor for MK0677 was characterized in the plasma membrane fraction of pituitary and hypothalamic tissue. The receptor is present in very low abundance and couples to phospholipase C. Other ligands selective for this receptor also cause synchronization of well-defined pathways leading to GH release. Repeated oral treatment of dogs once daily with MK0677 initiates amplified pulsatile GH release accompanied by increases in IGF-1 that are sustained. The unique biological properties of MK0677 and other synthetic ligands that bind to the same receptor force us to predict that these ligands mimic a naturally occurring hormone that regulates pulsatile GH release. Understanding the regulatory mechanisms involved in this paradigm has broad implications for the control of pulsatile rhythms in the endocrine system.
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PMID:Modulation of pulsatile GH release through a novel receptor in hypothalamus and pituitary gland. 870 Oct 83


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