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)

Recently, we have reported in immature female rats that short-term blockade of glutamate receptors of the N-methyl-D-aspartic acid (NMDA) subtype by the noncompetitive antagonist MK-801 induced a reduction of growth rate, basal and stimulated growth hormone (GH) release and plasma somatomedin C levels. In the present study, we investigated in immature male rats the mechanism(s) through which agonists and antagonists of glutamate receptors affect GH secretion. In 21-day-old male rats, administration of MK-801 (0.2 mg/kg i.p.b.i.d.) for 10 days induced a significant impairment of growth rate, which was unrelated to a significant reduction of food intake. GH secretion from anterior pituitary fragments of MK-801-treated rats was not significantly reduced under basal conditions but was significantly less under stimulation by 40 mM K+. Incubation of dispersed pituitary cells of 31-day-old rats with N-methyl-aspartic acid (1 and 100 microM), alone or associated with MK-801 (1 microM) did not change GH secretion. Semi quantitative densitometric analysis of hypothalami of MK-801-treated rats evidenced a clearcut decrease in the intensity of GHRH-like immuno-reactivity (LI) staining in the median eminence (ME), whereas no difference was observed in the ME-somatostatin (SS)-LI. Finally, GHRH mRNA but not SS-mRNA, evaluated by slot-blot hybridization, was reduced in the hypothalamus of MK-801-treated rats. These and our previous data would demonstrate that NMDA glutamate receptors play an important role in the neuroendocrine control of GH secretion in the rat, and suggest an action mediated by GHRH-secreting neurons.
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PMID:Central mechanisms subserving the impaired growth hormone secretion induced by persistent blockade of NMDA receptors in immature male rats. 134 48

The diagnosis of nesidioblastosis was established in a 9-month-old male child with a history of recurrent convulsive seizures and hypoglycemia. After unsuccessful subtotal pancreatectomy, treatment was started with the long-acting somatostatin derivative Sandostatin (Octreotide, Sandoz) at a dosage of 25 micrograms t.i.d. spaced between carbohydrate-enriched meals. With this regime, blood glucose was maintained at the low normal range and seizures ceased. During a 30-month observation period, growth velocity and weight progression were well within the predicted limits. A 24-hour hormone profile recorded at the end of the observation period revealed the following: (1) failure to improve blood glucose with carbohydrate-enriched food due to reactive hyperinsulinemia; (2) hyperglycemic reaction after administration of Sandostatin caused by a reduction of plasma insulin; this effect was particularly marked during sleep; (3) low mean GH, decreased spiking frequency and reduced area covered by the nocturnal peaks by recognized standards, and (4) normal somatomedin C levels for age. Interpretation of growth hormone (GH) data is hindered by the lack of pertinent information from the patient's age group. Recording of normal growth progression in the case illustrated here can only be explained by the capability of a reduced GH secretory rate to maintain full biological activity as shown by the normal plasma level of somatomedin C. Indeed, recent evidence has been provided elsewhere for normal growth progression in the presence of low GH secretion, although other factors unrelated to this hormone may also be operative at this early age. Further reports concerning the treatment of non-GH-dependent conditions with somatostatin derivatives will certainly contribute to the better understanding of the mechanisms governing growth in the postnatal period.
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PMID:Growth progression and 24-hour hormone profile in an infant treated chronically with a long-acting somatostatin derivative. 168 92

The effect of caloric restriction (CR) on the growth hormone (GH) response to compounds reportedly capable of acting via somatostatinergic influences, i.e. cholinergic agonist or antagonist drug, glucose or thyrotropin-releasing hormone (TRH), administered alone or combined with GH-releasing hormone (GHRH), was evaluated in dogs. Eight beagle dogs, aged 4-5 years, underwent a 26-day period of increasing CR; they were evaluated either under basal conditions or starting from day 13 of CR, according to a schedule which allowed the mean length of CR to be similar among individual tests. CR resulted in a significant increase in basal GH levels, and starting from day 13 in a significant decrease in plasma somatomedin C levels; plasma glucose levels were significantly diminished on day 13 of CR and then remained unaltered. Administration of GHRH (GHRH1-44, 2 micrograms/kg, i.v.) induced a rise in plasma GH levels strikingly higher during CR than under basal conditions. Pyridostigmine (2 mg/kg orally), a muscarinic cholinergic agonist reportedly capable of restraining hypothalamic release of somatostatin (SS), enhanced the GH response to GHRH under basal conditions, but failed to do so during CR. Conversely, pirenzepine (0.6 mg/kg, i.v.), a muscarinic cholinergic antagonist, abolished the GHRH-induced GH rise under basal conditions, but only reduced it during CR. Only by doubling the dose of pirenzepine was complete inhibition of the GHRH-induced GH rise effected. Glucose alone (2 g/kg, p.o.) failed to modify basal GH secretion either before or during CR, but significantly inhibited the GHRH-induced GH rise either before or during CR.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Studies of growth hormone secretion in calorically restricted dogs: effect of cholinergic agonists and antagonists, glucose and thyrotropin-releasing hormone. 190 62

The medical treatment of acromegaly with dopaminergic drugs has its physiopathological premise in the observation that agents capable of stimulating dopaminergic receptors directly are capable of determining GH secretion inhibition in a large percentage of acromegalic patients. Chronic administration of 5-20 mg/die of bromocryptin, long acting dopaminergic agonist, leads to a stable reduction in the levels of GH and somatomedin C (SmC) in about 50% of patients. However, these are only normalised in 20%. Treatment induces marked improvement in the clinical and metabolic changes typical of acromegalic disease. The therapeutic effect of dopaminergics may be maintained for periods of treatment lasting years but upon suspension of treatment pH levels return quickly to pretreatment levels. The antitumoral effect of the dopaminergic frequently encountered in prolactinomas is a rarer event in acromegaly and occurs more readily in patients with mixed secreting GH and PRL tumours than in pure GH. Currently octractide, a long lasting somatostatin analogue, is the most effective drug in the medical treatment of acromegaly; however the dopaminergic agonists remain a valid alternative.
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PMID:[Medical treatment of acromegaly with dopaminergic agents]. 198 Mar 33

Chronic hyperglycemia is the single most important pathogenic factor in the diabetic triad: retinopathy, glomerulopathy and neuropathy. But at equal serum glucose balance, diabetics are not equally at risk of microangiopathy. Hence the importance of timely screening of patients who should be convinced to accept the constraints and risk of perfect serum glucose balance or to whom specific therapy independent from serum glucose balance could be proposed. But at present, there is no genetic or immunologic marker allowing for the individual identification of at risk patients. Attention is thus directed towards factors which may be directly involved in the pathogenesis of diabetic microangiopathy: --Special sensitivity of vascular collagen to protein glycosylation which could be reflected in the involvement of tendon and aponeurotic collagen, --platelet abnormalities of which the exacerbating role appears to be confirmed by the significant efficacy of aspirin in the treatment of nonproliferative retinopathy in insulin-independent diabetics, --rheological abnormalities which might essentially be secondary to chronic hyperglycemia, --hormonal abnormalities, in particular hypersecretion of growth hormone and/or somatomedin C, whose role has long been suspected and could be established by therapeutic trials with new somatostatin analogues. But the most recent advances concern the study of hemodynamic factors. Irreversible organic diabetic microangiopathy is thought to be preceded by a phase of reversible functional microangiopathy, characterized by increased capillary blood flow, vascular dilatation, hyperpermeability and altered regulation of flow. Thus, diabetic glomerulopathy with decreased glomerular filtration is preceded by a phase of renal "hyperfunctioning" and irreversible proteinuria is the outcome of a progressive increase in microalbuminuria, reversible at least while the levels are not too high.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Screening of subjects at high risk for diabetic microangiopathies]. 264 89

In a previous study we demonstrated that the kidney content of somatomedin C was maximal one to two days after uninephrectomy or induction of diabetes, and that insulin treatment prevented an increase in kidney somatomedin C as well as kidney growth in diabetic animals. In the present study we have examined the effect of a somatostatin analogue on kidney somatomedin C and initial renal growth in the two experimental situations. The kidney hypertrophy in untreated diabetic animals amounted to 23% four days after streptozotocin injection and followed an increase in kidney somatomedin C content of 60% reaching the maximum after 48 h. In young and old uninephrectomized rats kidney growth was 19% and 16% after four days. In young animals a prompt increase of 50% in kidney somatomedin C was seen as reaching the maximum after 24 h, while the somatomedin C content in kidneys from old animals was maximal after 48 h (increase of 58%) in good accordance with the slightly slower kidney growth. The new findings of the present study are that administration of a long-acting somatostatin analogue (Sandostatin) effectively prevented the obligatory increase in kidney somatomedin C content as well as kidney growth both in experimental diabetes and after uninephrectomy. It is noteworthy that Sandostatin administration did not alter the metabolic state in diabetic animals indicating that the inhibition of kidney hypertrophy could not be attributed to improved metabolic control. The results thus support the concept that somatomedin C is involved in initial diabetic and post-nephrectomy renal growth.
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PMID:Somatostatin analogue administration prevents increase in kidney somatomedin C and initial renal growth in diabetic and uninephrectomized rats. 275 63

This study examined the effects of the long-acting selective mini somatostatin analogue (SMS) 201-995 in two acromegalic patients who were treated for 3 and 6 months, respectively. During treatment the mean growth hormone levels (25.3 and 20.8 ng/ml vs 5.9 and 10.6 ng/ml) and somatomedin C levels (6.2 and 6.2 IU/ml vs 3.3 and 3.8 IU/ml) decreased and the patients reported an improvement in their symptoms. The main side effect was an increase in stool fat excretion which did exceed the normal range (less than 7 g/day) in one patient. Five acromegalics who received 2 X 50 micrograms SMS 201-995/day for 5 days showed a significant increase of stool fat excretion (1.7 vs 3.5 g/day; p less than 0.05). Fasting blood glucose levels, glucose tolerance, and glycosylated hemoglobin were not essentially effected. It is concluded that SMS 201-995 offers new possibilities in the treatment of acromegaly. The gastrointestinal and diabetogenic side effects of this substance, however, should be carefully monitored.
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PMID:Long-term treatment of acromegaly with the somatostatin analogue SMS 201-995 over 6 months. 287 Dec 21

We have recently obtained encouraging short-term results after a single subcutaneous injection of the long-acting somatostatin analogue SMS 201-995 in acromegalic patients. Increased growth hormone (GH) levels may be involved in the pathogenesis of proliferative retinopathy in type I diabetes mellitus. In this study we thus investigated the effect of 3 X 50 micrograms SMS 201-995 daily on the metabolic control and hormone secretion of eight type I diabetics over a 3-day period. GH levels decreased by 32% (p less than 0.05) and somatomedin C levels by 31% (p less than 0.01) on the 3rd day of treatment compared with a control day. The insulin requirements during conventional subcutaneous insulin therapy were reduced by 28% (p less than 0.01) in seven patients without deterioration of metabolic control (mean blood glucose levels, 153.8) versus 154.7 mg/dl). Triiodothyronine, thyroxine, glucagon, prolactin, luteinizing hormone and follicle-stimulating hormone showed no significant changes. We conclude that SMS 201-995 could be an excellent tool for further clinical investigation and therapy of diabetic vascular complications.
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PMID:Somatostatin analogue SMS 201-995 in type I diabetes mellitus. Initial experience after repeated administration. 287 2

The effect of a new long-acting somatostatin analog SMS 201-995 (SMS) on hormonal mechanisms controlling the glucose metabolism was tested in 8 type I diabetics over a 3-day period. In addition to dietary measures and conventional insulin therapy, the patients received a subcutaneous dose of 50 micrograms SMS three times daily for 3 days. Serum growth hormone (GH) was measured at various intervals throughout the investigational period. Glucagon, somatomedin C (SM-C), triiodothyronine, thyroxine, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin (PRL) were also determined before and at the end of the therapy with SMS. Basal GH and plasma SM-C had decreased significantly (p less than 0.05 and p less than 0.01, respectively) by the 3rd day. In all cases the insulin requirements could be reduced (mean 28%) without deterioration of the metabolic control. Moreover, blood glucose profiles showed a tendency to lower postprandial peaks after SMS treatment. Glucagon, triiodothyronine, thyroxine, LH, FSH and PRL showed no significant changes. No side effects or alterations in laboratory chemistries were recorded. Dampening of glucose oscillations and counterregulatory mechanisms, and reduction of insulin dosage by SMS may enable a better control of unstable diabetes. Its slow plasma clearance and long action compared to the native peptide will warrant the use of this analog as a additive to standard diabetes therapy in more prolonged trials.
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PMID:Suppression of growth hormone and somatomedin C by long-acting somatostatin analog SMS 201-995 in type I diabetes mellitus. 288 4

A 26-year-old man with acromegaly secondary to ectopic growth hormone-releasing hormone (GHRH) secretion by a metastatic carcinoid tumor is the subject of this study. He previously failed to respond to conventional therapeutic modalities (partial hypophysectomy, pituitary irradiation, high-dose bromocriptine and a combination of streptozotocin and 5-fluorouracil) and was treated with long-acting somatostatin analogue SMS 201-995 (Sandoz, East Hanover, NJ). Growth hormone and somatomedin C concentrations became normal, and GHRH-LI (GHRH-like immunoreactivity) was suppressed by more than 60%. The growth hormone response to exogenous GHRH 1-40 was stopped and growth hormone rise to thyrotropin-releasing hormone (TRH) was significantly attenuated. A significant shrinkage of the pituitary gland was observed. Similarly, the size of the metastatic carcinoid lesions decreased dramatically and was accompanied by a normalization of liver function. After almost 2 years of SMS 201-995 therapy, the patient was well and had no clinical signs of acromegaly. Thus, SMS 201-995 appears to be a remarkably effective agent for treatment of acromegaly secondary to ectopic GHRH secretion.
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PMID:Acromegaly from ectopic growth hormone-releasing hormone secretion by a malignant carcinoid tumor. Successful treatment with long-acting somatostatin analogue SMS 201-995. 289 32


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